A NOVEL INTERLEUKIN-1 RECEPTOR ANTAGONIST AND USES THEREOF

Abstract: The present invention provides novel nucleic acids, the novel polypeptide sequences encoded by these nucleic acids and uses thereof. These novel polynucleotide and polypeptide sequences were determined to be a novel Interleukin-1 Receptor Antagonist.

Description: A NOVEL INTERLEUKIN - 1 RECEPTOR ANTAGONIST AND USES THEREOF 1. RELATED APPLICATIONS This patent application is a continuation-in-part of U.S. patent application 09/576,008 filed May 22, 2000, which is a continuation-in-part of U.S. patent application Serial No. 09/523,552 (Attorney docket no. 28110/36211) filed March 10, 2000, which is a continuation-in-part of U.S. patent application Serial No. 09/457,626 filed December 8, 1999, which is a continuation-in-part of U.S. patent application Serial No. 09/417,455 filed October 13, 1999 which is a continuation-in-part of U.S. patent application Serial No. 09/348,942 filed July 7, 1999 which is a continuation-in- part of U.S. patent application Serial No. 09/287,210 filed April 5, 1999 which is a continuation-in-part of U.S. patent application Serial No. 09/251,370 (Attorney Docket No. 20411-755) filed February 17, 1999 which is a continuation-in-part of U.S. patent application Serial No. 09/127,698 (Attorney Docket No. 20411-749), filed July 31, 1998, and a continuation-in-part of U.S. patent application Serial No. 09/229,591 (Attorney Docket No. 20411-743 CON1) filed January 13, 1999, which is a continuation of U.S. patent application Serial No. 09/099,818 (Attorney Docket No. 20411-743) filed June 19, 1998. U.S. patent application Serial No. 09/127,698 (Attorney Docket No. 20411-749) and U.S. patent application Serial No. 09/099,818 (Attorney Docket No. 20411-743) are continuations in part of U.S. patent application Serial No. 09/082,364 (Attorney Docket No. 20411-738), filed May 20, 1998, which is a continuation- in-part of U.S. patent application Serial No. 09/079,909 (Attorney Docket No. 20411-737), filed May 15, 1998, which is a continuation-in-part of U.S. patent application Serial No. 09/055,010 (Attorney Docket No. 20411-733), filed April 3, 1998, all of which are incoφorated by reference herein in their entirety. 2. FIELD OF THE INVENTION The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins. 3. BACKGROUND Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, CSFs, chemokines, and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques clone novel polynucleotides "directly" in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence ofthe protein in the case of hybridization cloning; activity ofthe protein in the case of expression cloning). More recent "indirect" cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well- recognized secretory leader sequence motif, as well as various PCR-based or low stringency hybridization cloning techniques, have advanced the state ofthe art by making available large numbers of DNA amino acid sequences for proteins that are known to have biological activity by virtue of their secreted nature in the case of leader sequence cloning, or by virtue of the cell or tissue source in the case of PCR-based techniques. It is to these proteins and the polynucleotides encoding them that the present invention is directed. In particular, this invention is directed to a novel Interleukin- 1 Receptor Antagonist. Cytokines, such as Interleukin- 1, are well known to cause morphological and functional alterations in endothelial cells. These alterations occur in part as a result of "endothelial cell activation" Distinct immune-mediators such as tumor necrosis factor (TNF), interleukin- 1 (Interleukin- 1), and gamma-interferon (TFN) appear to induce different but partially overlapping patterns of endothelial cell activation including increased procoagulant activity (Bevilaqua (1986) PNAS, 83:4533-4537), PGI and 2 production (Rossi (1985), Science, 229:174-176), HLA antigen expression (Pober (1987) J. Immunol., 138:3319-3324) and lymphocyte adhesion molecules (Carender (1987) J. Immunol., 138:2149-2154). These cytokines are also reported to cause hypotension, vascular hemorrhage, and ischemia (Goldblum et al. 1989, Tracey et al. Science 234:470, 1986). A major dose limiting toxicity of these and other biological response modifiers is hypotension and vascular leakage (Dvorak (1989) J.N.C.I., 81:497-502). The ability of IL-1 to modify biological responses has been demonstrated in a variety of studies. For example, the administration of Interleukin- 1 to rabbits (Wakabayashi et al., FASEB J 1991;5:338; Okusawa et al. J Clin Invest 1988;81 :1162; Ohlsson et al., Nature 1990;348:550; Aiura, et al. Cytokine 1991;4:498) and primates (Fischer et al. Am J Physiol 1991;261:R442) has been shown to result in hypotension, tachycardia, lung edema, renal failure, and, eventually, death, depending on the dose. When the serum from the Interleukin- 1 treated animals is examined, the elevation of other cytokines is evident, mimicking the levels seen in acute pancreatitis in humans. (Guice et al., J Surg Res 1991;51:495-499; Heath et al., Pancreas 1993;66:41-45) There is a large body of evidence currently available which supports the role of Interleukin-1 as a major mediator ofthe systemic response to diseases such as sepsis and pancreatitis and as an activator ofthe remaining members ofthe cytokine cascade. (Dinarello et al., Arch Surg 1992;127:1350-1353). The cytokine Interleukin-1 is a key mediator in the inflammatory response (for reviews, see Dinarello (1991) Blood 77: 1627-1652; Dinarello et al. (1993) New England J. Med. 328:106-113; Dinarello (1994) FASEB J. 8:1314-1325). The importance of Interleukin-1 in inflammation has been demonstrated by the ability of the highly specific Interleukin-1 receptor antagonist protein to relieve inflammatory conditions (for review, see Dinarello (1991) Blood 77: 1627-1652; Dinarello et al. (1993) New England J. Med. 328:106-113; Dinarello (1994) FASEB J. 8:1314-1325; Dinarello (1993) Immunol. Today 14:260-264). Many ofthe proinflammatory effects of Interleukin-1, such as the upregulation of cell adhesion molecules on vascular endothelia, are exerted at the level of transcriptional regulation. The transcriptional activation by Interleukin-1 of cell adhesion molecules and other genes involved in the inflammatory response appears to be mediated largely by NF- kappa B (Shirakawa et al. (1989) Mole. Cell Biol. 9:2424-2430; Osborn et al., (1989) Proc. Natl. Acad. Sci. USA 86:2336-2340; Krasnow et al., (1991) Cytokine 3:372-379; Collins et al., (1993) Trends Cardiovasc. Med. 3:92-97). In response to Interleukin-1, the NF- kappa B inhibitory factor I kappa B is degraded and NF- kappa B is released from its inactive cytoplasmic state to localize within the nucleus where it binds DNA and activates transcription (Liou et al. (1993) Curr. Opin. Cell Biol. 5:477-487; Beg et al., (1993) Mol. Cell. Bid. 13:3301-3310). Interleukin-1 is also a mediator of septic shock . Septic shock, a life-threatening complication of bacterial infections, affects 150,000 to 300,000 patients annually in the United States (Parrillo, J. E. (1989), Septic Shock in Humans: Clinical Evaluation, Pathogenesis, and Therapeutic Approach (2nd ed.) In: Textbook of Critical Care Shoemaker, et al., editors, Saunders Publishing Co., Philadelphia, Pa., pp. 1006). The cardiovascular collapse and multiple metabolic derangements associated with septic shock are due largely to bacterial endotoxin (ET), which has been shown to elicit a septic shock-like condition when administered to animals (Natanson, et al. (1989), Endotoxin and Tumor Necrosis Factor Challenges in Dogs Simulate the Cardiovascular Profile of Human Septic Shock, J. Exp. Med. 169:823). Thus, there is a great need for modulators of Interleukin-1. 4. SUMMARY OF THE INVENTION The compositions ofthe present invention include novel isolated polypeptides, in particular, novel Interleukin-1 Receptor Antagonist proteins (referred to hereafter as JX-lHyl or LL-1 Hyl receptor antagonist), isolated polynucleotides encoding such polypeptides, including recombinant DNA molecules, cloned genes or degenerate variants thereof, especially naturally occurring variants such as allelic variants, and antibodies that specifically recognize one or more epitopes present on such polypeptides. The compositions ofthe present invention additionally include vectors, including expression vectors, containing the polynucleotides ofthe invention, cells genetically engineered to contain such polynucleotides and cells genetically engineered to express such polynucleotides. The isolated polynucleotides ofthe invention include, but are not limited to, a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 3 or 5. The isolated polynucleotides ofthe invention further include, but are not limited to, a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 1, 2, 4, or 6; a polynucleotide comprising the full length protein coding sequence of SEQ ID NO: 1, 2, 4, or 6, and; a polynucleotide comprising the nucleotide sequence ofthe mature protein coding sequence of SEQ ID NO: 1, 2, 4, or 6. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes to the complement ofthe nucleotide sequence of SEQ ID NO: 1, 2, 4, or 6 under stringent hybridization conditions; a polynucleotide which is an allelic variant of any polynucleotide recited above; a polynucleotide which encodes a species homolog of any ofthe proteins recited above; or a polynucleotide that encodes a polypeptide comprising a specific domain or truncation ofthe polypeptide of SEQ ID NO: 1, 2, 4, or 6. The isolated polynucleotides ofthe invention further include, but are not limited to a polynucleotide comprising the nucleotide sequence ofthe genomic clone SEQ LD NO: 7 or 8; a polynucleotide assembled from one or more ofthe exons of SEQ ID NO: 7 or 8; a polynucleotide assembled from one or more ofthe introns of SEQ ID NO: 7 or 8; a polynucleotide assembled from one or more ofthe exons of SEQ ID NO: 7 or 8 and one or more ofthe introns of SEQ ID NO: 7 or 8; a polynucleotide comprising the full length protein coding sequence of SEQ ID NO: 7 or 8; a polynucleotide comprising the nucleotide sequence ofthe mature protein coding sequence of SEQ ID NO: 7 or 8. The polynucleotides ofthe present invention also include, but are not limited to, a polynucleotide that hybridizes to the complement ofthe nucleotide sequence of SEQ ID NO: 7 or 8 under stringent hybridization conditions; a polynucleotide that hybridizes to the complement of any one ofthe introns or exons of SEQ ID NO: 7 or 8 under stringent hybridization conditions; a polynucleotide which is an allelic variant of any polynucleotide recited above; a polynucleotide which encodes a species homolog of any ofthe proteins recited above; or a polynucleotide that encodes a polypeptide comprising a specific domain or truncation ofthe polypeptide of SEQ ID NO: 7 or 8. The polynucleotides ofthe present invention still further include, but are not limited to, a polynucleotide comprising the nucleotide sequence ofthe cDNA insert of clone pIL-lHy273 deposited with the American Type Culture Collection (ATCC; 10801 University Blvd., Manassas, Virginia, 20110-2209, U.S.A.); a polynucleotide comprising a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 3 or 5 which polynucleotide is assembled from the cDNA insert of clone pIL-lHy273; a polynucleotide comprising the full length protein coding sequence of SEQ ID NO: 3 or 5 which polynucleotide is assembled from the cDNA insert of clone pIL-lHy273;or, a polynucleotide comprising the nucleotide sequence ofthe mature protein coding sequence of SEQ ID NO: 3 or 5. The polynucleotides ofthe invention additionally include the complement of any ofthe polynucleotides recited above. A collection as used in this application can be a collection of only one polynucleotide. The collection of sequence information or identifying information of each sequence can be provided on a nucleic acid array. In one embodiment, segments of sequence information are provided on a nucleic acid array to detect the polynucleotide that contains the segment. The array can be designed to detect nucleic acids that are perfectly complementary (full-match) or mismatched to the polynucleotide that contains the segment. The collection can also be provided in a computer-readable format. The isolated polypeptides ofthe invention include, but are not limited to, a polypeptide comprising the amino acid sequence of SEQ ID NO: 3 or 5, a full length protein of SEQ ID NO: 3 or 5; a mature protein coding sequence of SEQ ID NO: 5, preferably having a molecular mass as determined by SDS-PAGE of about 16 or 17 kDa, or less. Alternatively polypeptides ofthe invention have a have a molecular mass by SDS-PAGE of about 15.5 or about 16.5 kDa; or a polypeptide encoded by one or more ofthe exons of SEQ ID NO: 7 or 8. The polypeptides ofthe present invention further include, but are not limited to, a polypeptide comprising the amino acid sequence encoded by the cDNA insert of clone pIL-lHy273 deposited with the American Type Culture Collection (ATCC; 10801 University Blvd., Manassas, Virginia, 20110-2209, U.S.A.); a full length protein of SEQ ID NO: 3 or 5 assembled from the amino acid sequence encoded by the cDNA insert of clone pIL-lHy273; or, a mature protein coding sequence of SEQ ID NO: 3 or 5 assembled from the amino acid sequence encoded by cDNA insert of clone pIL-lHy273, preferably having a molecular mass as determined by SDS-PAGE of about 16 kDa, or less, more preferably, having a molecular mass by SDS-PAGE of about 15.5 kDa. Protein compositions ofthe present invention may further comprise an acceptable carrier, such as a hydrophilic, e.g., pharmaceutically acceptable, carrier. The invention also relates to methods for producing a polypeptide comprising growing a culture ofthe cells ofthe invention in a suitable culture medium, and purifying the protein from the culture. Preferred embodiments include those in which the protein produced by such process is a mature form ofthe protein. Polynucleotides according to the invention have numerous applications in a variety of techniques known to those skilled in the art of molecular biology. These techniques include use as hybridization probes, use as oligomers for PCR, use for chromosome and gene mapping, use in the recombinant production of protein, and use in generation of anti-sense DNA or RNA, their chemical analogs and the like. For example, when the expression of an mRNA is largely restricted to a particular cell or tissue type, polynucleotides ofthe invention can be used as hybridization probes to detect the presence ofthe particular cell or tissue mRNA in a sample using, e.g., in situ hybridization. In other exemplary embodiments, the polynucleotides are used in diagnostics as expressed sequence tags for identifying expressed genes or, as well known in the art and exemplified by Vollrath et al., Science 258:52-59 (1992), as expressed sequence tags for physical mapping ofthe human genome. The polypeptides according to the invention can be used in a variety of conventional procedures and methods that are currently applied to other proteins. For example, a polypeptide ofthe invention can be used to generate an antibody that specifically binds the polypeptide. The polypeptides ofthe invention can also be used as molecular weight markers, and as a food supplement. Methods are also provided for preventing, treating or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition comprising a protein ofthe present invention and a pharmaceutically acceptable carrier. In particular, the polypeptides and polynucleotides ofthe invention can be utilized, for example, as part of methods for the prevention and/or treatment of disorders involving sepsis, acute pancreatitis, endotoxic shock, cytokine induced shock, rheumatoid arthritis, chronic inflammatory arthritis, pancreatic cell damage from diabetes mellitus type 1 , graft versus host disease, inflammatory bowel disease, inflamation associated with pulmonary disease, other autoimmune disease or inflammatory disease, allergies or bronchitis (including chronic allergies and chronic bronchitis), an antiproliferative agent such as for acute or chronic myelogenous leukemia or in the prevention of premature labor secondary to intrauterine infections. Treatment of inflammation resulting from allergic reactions or acute or chronic infections (caused by viral, bacterial, fungal, protozoan or other organisms) is specifically contemplated. The methods ofthe present invention further relate to methods for detecting the presence ofthe polynucleotides or polypeptides ofthe invention in a sample. Such methods can, for example, be utilized as part of prognostic and diagnostic evaluation of disorders as recited above and for the identification of subjects exhibiting a predisposition to such conditions. Furthermore, the invention provides methods for evaluating the efficacy of drugs, and monitoring the progress of patients, involved in clinical trials for the treatment of disorders as recited above. The invention also provides methods for the identification of compounds that modulate the expression ofthe polynucleotides and/or polypeptides ofthe invention. Such methods can be utilized, for example, for the identification of compounds that can ameliorate symptoms of disorders as recited above. Such methods can include, but are not limited to, assays for identifying compounds and other substances that interact with (e.g., bind to) the polypeptides ofthe invention. The methods ofthe invention also include methods for the treatment of disorders as recited above which may involve the administration of such compounds to individuals exhibiting symptoms or tendencies related to disorders as recited above. In addition, the invention encompasses methods for treating diseases or disorders as recited herein by administering compounds and other substances that modulate the overall activity ofthe target gene products. Compounds and other substances can effect such modulation either on the level of target gene expression or target protein activity. The invention also specifically provides methods of treating an inflammatory disease state mediated by IL-18 comprising administering to a subject in need thereof an amount of LL-1 Hyl polynucleotide, polypeptide or agonist ofthe invention effective to inhibit IL-18 activity. Also provided are in vitro and in vivo methods of inhibiting IL-18 activity. 5. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows the sequence alignment of SEQ ID NO: 3 with human (SEQ ID NO: 30), mouse (SEQ ID NO: 9), rat (SEQ ID NO: 10) and rabbit Interleukin-1 receptor antagonist (SEQ ID NO: 11). A- Alanine; R- Arginine; - Asparagine; D- Aspartic Acid; C- Cysteine; E- Glutamic Acid; Q- Glutamine; G- Glycine; H- Histidine; I- Isoleucine; L- Leucine; K- Lysine; — Methionine; F- Phenylalanine; P- Proline; S- Serine; T- Threonine; W- Tryptophan; Y- Tyrosine; V- Valine; X - any of the twenty amino acids. Gaps are presented as dashes. Amino acid numbers for all four sequences are labeled accordingly. FIG. 2 shows the nucleic acid sequences that were obtained from the b 2 HFLS20W cDNA library using standard PCR, sequencing by hybridization signature analysis, and single pass gel sequencing technology. These sequences are designated as SEQ ID NOS: 1 and 2. A- adenosine; C-cytosine; G-guanosine; T-thymine; and N-any ofthe four bases. FIG. 3 shows the amino acid sequences which correspond to nucleotides 1 through 240 of SEQ ED NO: 2. These sequences are designated as SEQ ID NO: 3. A- Alanine; R- Arginine; - Asparagine; D- Aspartic Acid; C- Cysteine; E- Glutamic Acid; Q- Glutamine; G- Glycine; H- Histidine; I- Isoleucine; L- Leucine; K- Lysine; — Methionine; F- Phenylalanine; P- Proline; S- Serine; T- Threonine; W- Tryptophan; Y- Tyrosine; V- Valine; X - any ofthe twenty amino acids. FIG. 4 shows the sequence alignment of receptor binding regions of human Interleukin-1 beta (SEQ ID NO: 12) and human Interleukin-1 receptor antagonist (SEQ ID NO: 13)aligned with a cognate region of SEQ ID NO:3 (amino acids 13 through 30 of SEQ ID NO:3). Residues conserved among all three domains are shown in boldface. FIG. 5 shows the nucleic acid sequence designated SEQ ID NO: 4 (nucleotides 297 through 1282 of SEQ LO NO: 4 correspond to SEQ ID NO: 2) and are described in Example 6 . The first eleven nucleic acid sequences correspond to vector sequence. FIG. 6 shows the amino acid sequence encoded by SEQ ID NO: 4 (amino acids 76 through 155 of SEQ ID NO: 5 correspond to SEQ ID NO; 3). This amino acid sequence is designated SEQ DD NO: 5 and is described in Example 6. FIG. 7 presents an amino acid alignment of SEQ ID NO: 5 (amino acids 1 through 155 of SEQ ED NO: 5) with the cytoplasmic form of human IL-1 Ra ( SEQ DD NO: 14; labeled "HUMILIRASIC"). The homology between these two sequences is discussed in Example 6. FIG. 8 shows SEQ DD NO: 6 which represents an extension (the underlined sequence) ofthe nucleic acid sequence corresponding to SEQ DD NO: 4 and is described in Example 7. FIGS 9A-C show the genomic sequence corresponding to SEQ DD NOS: 1, 2, and 4 6. The isolation ofthe genomic clone (SEQ DD NO: 7 ) from which this sequence was derived is described in Example 8. A- adenosine; C-cytosine; G-guanosine; T-thymine. Ambiguous positions are designated as follows: R indicates A or G; M indicates A or C; W indicates A or T; Y indicates C or T; S indicates C or G; K indicates G or T; V indicates A or C or G; H indicates A or C or T; D indicates A or G or T; B indicates C or G or T; and N indicates any ofthe four bases. FIGS 10A-C show a genomic clone (SEQ DD NO: 8) which is an extension of the genomic sequence presented in Figure 9A-C (SEQ DD NO: 7). SEQ ED NO: 8 includes the extended sequence shown in SEQ DD NO: 6 for the Interleukin-1 Receptor Antagonist extension presented in SEQ DD NO: 6. The isolation of this genomic clone (SEQ DD NO: 7 ) from which this sequence was derived is described in Example 11. A- adenosine; C-cytosine; G-guanosine; T-thymine. Ambiguous positions are designated as follows: R indicates A or G; M indicates A or C; W indicates A or T; Y indicates C or T; S indicates C or G; K indicates G or T; V indicates A or C or G; H indicates A or C or T; D indicates A or G or T; B indicates C or G or T; and N indicates any ofthe four bases. FIG. 11 shows the dose dependent ability of IL-lHyl to inhibit IL-lβ induced PGE 2 production. 6. DETAILED DESCRIPTION 6.1. DEFINITIONS The term "nucleotide sequence" refers to a heteropolymer of nucleotides or the sequence of these nucleotides. The terms "nucleic acid" and "polynucleotide" are also used interchangeably herein to refer to a heteropolymer of nucleotides. Generally, nucleic acid segments provided by this invention may be assembled from fragments of the genome and short oligonucleotide linkers, or from a series of oligonucleotides, or from individual nucleotides, to provide a synthetic nucleic acid which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon, or a eukaryotic gene. The terms "oligonucleotide fragment" or a "polynucleotide fragment", "portion," or "segment" is a stretch of polypeptide nucleotide residues which is long enough to use in polymerase chain reaction (PCR) or various hybridization procedures to identify or amplify identical or related parts of mRNA or DNA molecules. The terms "oligonucleotides" or "nucleic acid probes" are prepared based on the polynucleotide sequences provided in the present invention. Oligonucleotides comprise portions of such a polynucleotide sequence having at least about 15 nucleotides and usually at least about 20 nucleotides. Nucleic acid probes comprise portions of such a polynucleotide sequence having fewer nucleotides than about 6 kb, usually fewer than about 1 kb. After appropriate testing to eliminate false positives, these probes may, for example, be used to determine whether specific mRNA molecules are present in a cell or tissue or to isolate similar nucleic acid sequences from chromosomal DNA as described by Walsh et al. (Walsh, P.S. et al., 1992, PCR Methods Appl 1:241-250). The term "probes" includes naturally occurring or recombinant or chemically synthesized single- or double-stranded nucleic acids. They may be labeled by nick translation, Klenow fill-in reaction, PCR or other methods well known in the art. Probes ofthe present invention, their preparation and/or labeling are elaborated in Sambrook, J. et al., 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, NY; or Ausubel, F.M. et al., 1989, Current Protocols in Molecular Biology, John Wiley & Sons, New York NY, both of which are incorporated herein by reference in their entirety. The term "stringent" is used to refer to conditions that are commonly understood in the art as stringent. Stringent conditions can include highly stringent conditions (i.e., hybridization to filter-bound DNA under in 0.5 M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65°C, and washing in 0.1xSSC/0.1% SDS at 68°C), and moderately stringent conditions (i.e., washing in 0.2xSSC/0.1% SDS at 42°C). In instances wherein hybridization of deoxyoligonucleotides is concerned, additional exemplary stringent hybridization conditions include washing in 6xSSC/0.05% sodium pyrophosphate at 37°C (for 14-base oligos), 48°C (for 17-base oligos), 55°C (for 20-base oligos), and 60°C (for 23-base oligos). The term "recombinant," when used herein to refer to a polypeptide or protein, means that a polypeptide or protein is derived from recombinant (e.g., microbial or mammalian) expression systems. "Microbial" refers to recombinant polypeptides or proteins made in bacterial or fungal (e.g., yeast) expression systems. As a product, "recombinant microbial" defines a polypeptide or protein essentially free of native endogenous substances and unaccompanied by associated native glycosylation. Polypeptides or proteins expressed in most bacterial cultures, e.g., E. coli, will be free of glycosylation modifications; polypeptides or proteins expressed in yeast will have a glycosylation pattern in general different from those expressed in mammalian cells. The term "recombinant expression vehicle or vector" refers to a plasmid or phage or virus or vector, for expressing a polypeptide from a DNA (RNA) sequence. An expression vehicle can comprise a transcriptional unit comprising an assembly of (1) a genetic element or elements having a regulatory role in gene expression, for example, promoters or enhancers, (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate transcription initiation and termination sequences. Structural units intended for use in yeast or eukaryotic expression systems preferably include a leader sequence enabling extracellular secretion of translated protein by a host cell. Alternatively, where recombinant protein is expressed without a leader or transport sequence, it may include an N-terminal methionine residue. This residue may or may not be subsequently cleaved from the expressed recombinant protein to provide a final product. The term "recombinant expression system" means host cells which have stably integrated a recombinant transcriptional unit into chromosomal DNA or carry the recombinant transcriptional unit extrachromosomally. Recombinant expression systems as defined herein will express heterologous polypeptides or proteins upon induction ofthe regulatory elements linked to the DNA segment or synthetic gene to be expressed. This term also means host cells which have stably integrated a recombinant genetic element or elements having a regulatory role in gene expression, for example, promoters or enhancers. Recombinant expression systems as defined herein will express polypeptides or proteins endogenous to the cell upon induction of the regulatory elements linked to the endogenous DNA segment or gene to be expressed. The cells can be prokaryotic or eukaryotic. The term "open reading frame," ORF, means a series of nucleotide triplets coding for amino acids without any termination codons and is a sequence translatable into protein. The term "expression modulating fragment," EMF, means a series of nucleotides which modulates the expression of an operably linked ORF or another EMF. As used herein, a sequence is said to "modulate the expression of an operably linked sequence" when the expression ofthe sequence is altered by the presence ofthe EMF. EMFs include, but are not limited to, promoters, and promoter modulating sequences (inducible elements). One class of EMFs are fragments which induce the expression or an operably linked ORF in response to a specific regulatory factor or physiological event. As used herein, an "uptake modulating fragment," UMF, means a series of nucleotides which mediate the uptake of a linked DNA fragment into a cell. UMFs can be readily identified using known UMFs as a target sequence or target motif with the computer-based systems described below. The presence and activity of a UMF can be confirmed by attaching the suspected UMF to a marker sequence. The resulting nucleic acid molecule is then incubated with an appropriate host under appropriate conditions and the uptake ofthe marker sequence is determined. As described above, a UMF will increase the frequency of uptake of a linked marker sequence. The term "active" refers to those forms ofthe polypeptide which retain the biologic and/or immunologic activities of any naturally occurring polypeptide. The term "naturally occurring polypeptide" refers to polypeptides produced by cells that have not been genetically engineered and specifically contemplates various polypeptides arising from post-translational modifications ofthe polypeptide including, but not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation and acylation. The term "derivative" refers to polypeptides chemically modified by such techniques as ubiquitination, labeling (e.g., with radionuclides or various enzymes), pegylation (derivatization with polyethylene glycol) and insertion or substitution by chemical synthesis of amino acids such as ornithine, which do not normally occur in human proteins. The term "recombinant variant" refers to any polypeptide differing from naturally occurring polypeptides by amino acid insertions, deletions, and substitutions, created using recombinant DNA techniques. Guidance in determining which amino acid residues may be replaced, added or deleted without abolishing activities of interest, such as cellular trafficking, may be found by comparing the sequence ofthe particular polypeptide with that of homologous peptides and minimizing the number of amino acid sequence changes made in regions of high homology. Preferably, amino acid "substitutions" are the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, i.e., conservative amino acid replacements. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature ofthe residues involved. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. "Insertions" or "deletions" are typically in the range of about 1 to 5 amino acids. The variation allowed may be experimentally determined by systematically making insertions, deletions, or substitutions of amino acids in a polypeptide molecule using recombinant DNA techniques and assaying the resulting recombinant variants for activity. Alternatively, where alteration of function is desired, insertions, deletions or non-conservative alterations can be engineered to produce altered polypeptides. Such alterations can, for example, alter one or more ofthe biological functions or biochemical characteristics ofthe polypeptides ofthe invention. For example, such alterations may change polypeptide characteristics such as ligand-binding affinities, interchain affinities, or degradation/turnover rate. Further, such alterations can be selected so as to generate polypeptides that are better suited for expression, scale up and the like in the host cells chosen for expression. For example, cysteine residues can be deleted or substituted with another amino acid residue in order to eliminate disulfide bridges. As used herein, "substantially equivalent" can refer both to nucleotide and amino acid sequences, for example a mutant sequence, that varies from a reference sequence by one or more substitutions, deletions, or additions, the net effect of which does not result in an adverse functional dissimilarity between the reference and subject sequences. Typically, such a substantially equivalent sequence varies from one of those listed herein by no more than about 20% (i.e., the number of individual residue substitutions, additions, and or deletions in a substantially equivalent sequence, as compared to the corresponding reference sequence, divided by the total number of residues in the substantially equivalent sequence is about 0.2 or less). Such a sequence is said to have 80% sequence identity to the listed sequence. In one embodiment, a substantially equivalent, e.g., mutant, sequence ofthe invention varies from a listed sequence by no more than 10% (90% sequence identity); in a variation of this embodiment, by no more than 5% (95% sequence identity); and in a further variation of this embodiment, by no more than 2% (98% sequence identity). Substantially equivalent, e.g., mutant, amino acid sequences according to the invention generally have at least 95% sequence identity with a listed amino acid sequence, whereas substantially equivalent nucleotide sequence ofthe invention can have lower percent sequence identities, taking into account, for example, the redundancy or degeneracy of the genetic code. For the purposes ofthe present invention, sequences having substantially equivalent biological activity and substantially equivalent expression characteristics are considered substantially equivalent. For the purposes of determining equivalence, truncation ofthe mature sequence (e.g., via a mutation which creates a spurious stop codon) should be disregarded. Nucleic acid sequences encoding such substantially equivalent sequences, e.g., sequences ofthe recited percent identities, can routinely be isolated and identified via standard hybridization procedures well known to those of skill in the art. Where desired, an expression vector may be designed to contain a "signal or leader sequence" which will direct the polypeptide through the membrane of a cell. Such a sequence may be naturally present on the polypeptides ofthe present invention or provided from heterologous protein sources by recombinant DNA techniques. A polypeptide "fragment," "portion," or "segment" is a stretch of amino acid residues of at least about 5 amino acids, often at least about 7 amino acids, typically at least about 9 to 13 amino acids, and, in various embodiments, at least about 17 or more amino acids. To be active, any polypeptide must have sufficient length to display biologic and/or immunologic activity. In a preferred embodiment, the JL-lHyl fragment has a molecular weight as determined by SDS-PAGE of about 16 kDa or less. More preferably, the IL-lHyl fragment has a molecular mass of about 15.5 kDa. Alternatively, recombinant variants encoding these same or similar polypeptides may be synthesized or selected by making use ofthe "redundancy" in the genetic code. Various codon substitutions, such as the silent changes which produce various restriction sites, may be introduced to optimize cloning into a plasmid or viral vector or expression in a particular prokaryotic or eukaryotic system. Mutations in the polynucleotide sequence may be reflected in the polypeptide or domains of other peptides added to the polypeptide to modify the properties of any part ofthe polypeptide, to change characteristics such as ligand-binding affinities, interchain affinities, or degradation/turnover rate. The term "activated" cells as used in this application are those which are engaged in extracellular or intracellular membrane trafficking, including the export of neurosecretory or enzymatic molecules as part of a normal or disease process. The term "purified" as used herein denotes that the indicated nucleic acid or polypeptide is present in the substantial absence of other biological macromolecules, e.g., polynucleotides, proteins, and the like. In one embodiment, the polynucleotide or polypeptide is purified such that it constitutes at least 95% by weight, more preferably at least 99.8% by weight, ofthe indicated biological macromolecules present (but water, buffers, and other small molecules, especially molecules having a molecular weight of less than 1000 daltons, can be present). The term "isolated" as used herein refers to a nucleic acid or polypeptide separated from at least one other component (e.g., nucleic acid or polypeptide) present with the nucleic acid or polypeptide in its natural source. In one embodiment, the nucleic acid or polypeptide is found in the presence of (if anything) only a solvent, buffer, ion, or other component normally present in a solution ofthe same. The terms "isolated" and "purified" do not encompass nucleic acids or polypeptides present in their natural source. The term "infection" refers to the introduction of nucleic acids into a suitable host cell by use of a virus or viral vector. The term "transformation" means introducing DNA into a suitable host cell so that the DNA is replicable, either as an extrachromosomal element, or by chromosomal integration. The term "transfection" refers to the taking up of an expression vector by a suitable host cell, whether or not any coding sequences are in fact expressed. The term "intermediate fragment" means a nucleic acid between 5 and 1000 bases in length, and preferably between 10 and 40 bp in length. The term "secreted" includes a protein that is transported across or through a membrane, including transport as a result of signal sequences in its amino acid sequence when it is expressed in a suitable host cell. "Secreted" proteins include without limitation proteins secreted wholly (e.g., soluble proteins) or partially (e.g., receptors) from the cell in which they are expressed. "Secreted" proteins also include without limitation proteins which are transported across the membrane ofthe endoplasmic reticulum. "Secreted" proteins are also intended to include proteins containing non-typical signal sequences (e.g. Interleukin-1 Beta, see Krasney, P. A. and Young, P.R. (1992) Cytokine 4(2): 134 -143) and factors released from damaged cells (e.g. Interleukin-1 Receptor Antagonist, see Arend, W.P. et. al. (1998) Annu. Rev. Immunol. 16:27-55) Each ofthe above terms is meant to encompasses all that is described for each, unless the context dictates otherwise. NUCLEIC ACIDS AND POLYPEPTIDES OF THE INVENTION Nucleotide and amino acid sequences ofthe invention are reported below. Fragments ofthe proteins ofthe present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments ofthe protein may be in linear form or they may be cyclized using known methods, for example, as described in H. U. Saragovi, et al., Bio/Technology 10, 773-778 (1992) and in R. S. McDowell, et al., J. Amer. Chem. Soc. 114, 9245-9253 (1992), both of which are incorporated herein by reference. Such fragments may be fused to carrier molecules such as immunoglobulins for many purposes, including increasing the valency of protein binding sites. For example, fragments ofthe protein may be fused through "linker" sequences to the Fc portion of an immunoglobulin. For a bivalent form ofthe protein, such a fusion could be to the Fc portion of an IgG molecule. Other immunoglobulin isotypes may also be used to generate such fusions. For example, a protein-IgM fusion would generate a decavalent form ofthe protein ofthe invention. The present invention also provides both full-length and mature forms (for example, without a signal sequence or precursor sequence) ofthe disclosed proteins. The full-length form ofthe such proteins is identified in the sequence listing by translation ofthe nucleotide sequence of each disclosed clone. The mature form of such protein may be obtained by expression of the disclosed full-length polynucleotide in a suitable mammalian cell or other host cell. The sequence ofthe mature form ofthe protein is also determinable from the amino acid sequence ofthe full-length form. Where protein ofthe present invention is membrane bound, soluble forms ofthe protein are also provided. In such forms part or all ofthe regions causing the protein to be membrane bound are deleted so that the protein is fully secreted from the cell in which it is expressed. The present invention also provides genes corresponding to the cDNA sequences disclosed herein. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate genomic libraries or other sources of genomic materials. Species homologs ofthe disclosed polynucleotides and proteins are also provided by the present invention. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species. The invention also encompasses allelic variants ofthe disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms ofthe isolated polynucleotide which also encode proteins which are identical, homologous or related to that encoded by the polynucleotides. The compositions ofthe present invention include isolated polynucleotides, including recombinant DNA molecules, cloned genes or degenerate variants thereof, especially naturally occurring variants such as allelic variants, novel isolated polypeptides, and antibodies that specifically recognize one or more epitopes present on such polypeptides. Species homologs ofthe disclosed polynucleotides and proteins are also provided by the present invention. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species. The invention also encompasses allelic variants ofthe disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms ofthe isolated polynucleotide which also encode proteins which are identical, homologous or related to that encoded by the polynucleotides. 6.2 NUCLEIC ACIDS OF THE INVENTION The isolated polynucleotides ofthe invention include, but are not limited to, a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ DD NOS: 3 or 5. The isolated polynucleotides ofthe invention further include, but are not limited to a polynucleotide comprising the nucleotide sequence of SEQ DD NOS: 1 , 2, 4, or 6; a polynucleotide comprising the full length protein coding sequence of SEQ DD NOS: 1, 2, 4, or 6, and; a polynucleotide comprising the nucleotide sequence ofthe mature protein coding sequence of SEQ DD NOS: 1, 2, 4, or 6. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes to the complement ofthe nucleotide sequence of SEQ DD NOS: 1, 2, 4, or 6 under stringent hybridization conditions; a polynucleotide which is an allelic variant of any polynucleotide recited above; a polynucleotide which encodes a species homolog of any ofthe proteins recited above; or a polynucleotide that encodes a polypeptide comprising a specific domain or truncation ofthe polypeptide of SEQ DD NOS: 1, 2, 4, or 6. The isolated polynucleotides ofthe invention further include, but are not limited to a polynucleotide comprising the nucleotide sequence ofthe genomic clone SEQ DD NOS: 7 or 8; a polynucleotide assembled from one or more of the exons of SEQ DD NOS: 7 or 8 (e.g., alternative splicing) ; a polynucleotide assembled from one or more ofthe introns of SEQ DD NOS: 7 or 8; a polynucleotide assembled from one or more ofthe exons of SEQ DD NOS: 7 or 8 and one or more ofthe introns of SEQ DD NOS: 7 or 8; a polynucleotide comprising the full length protein coding sequence of SEQ DD NOS: 7 or 8; a polynucleotide comprising the nucleotide sequence ofthe mature protein coding sequence of SEQ DD NOS: 7 or 8. The polynucleotides ofthe present invention also include, but are not limited to, a polynucleotide that hybridizes to the complement ofthe nucleotide sequence of SEQ DD NOS: 7 or 8 under stringent hybridization conditions; a polynucleotide that hybridizes to the complement of any one ofthe introns or exons of SEQ DD NOS: 7 or 8 under stringent hybridization conditions; a polynucleotide which is an allelic variant of any polynucleotide recited above; a polynucleotide which encodes a species homolog of any ofthe proteins recited above; or a polynucleotide that encodes a polypeptide comprising a specific domain or truncation ofthe polypeptide of SEQ DD NOS: 7 or 8. The polynucleotides ofthe present invention still further include, but are not limited to, a polynucleotide comprising the nucleotide sequence ofthe cDNA insert of clone pIL-lHy273 deposited with the American Type Culture Collection (ATCC; 10801 University Blvd., Manassas, Virginia, 20110-2209, U.S.A.); a polynucleotide comprising a nucleotide sequence encoding the amino acid sequence of SEQ DD NO: 3 or 5 which polynucleotide is assembled from the cDNA insert of clone pIL-lHy273; a polynucleotide comprising the full length protein coding sequence of SEQ DD NO: 3 or 5 which polynucleotide is assembled from the cDNA insert of clone pIL-lHy273;or, a polynucleotide comprising the nucleotide sequence ofthe mature protein coding sequence of SEQ DD NO: 3 or 5. The polynucleotides ofthe invention additionally include the complement of any ofthe polynucleotides recited above. The polynucleotides ofthe invention also provide polynucleotides including nucleotide sequences that are substantially equivalent to the polynucleotides recited above. Polynucleotides according to the invention can have at least about 80%, more typically at least about 90%, and even more typically at least about 95%, sequence identity to a polynucleotide recited above. The invention also provides the complement ofthe polynucleotides including a nucleotide sequence that has at least about 80%, more typically at least about 90%, and even more typically at least about 95%, sequence identity to a polynucleotide encoding a polypeptide recited above. The polynucleotide can be DNA (genomic, cDNA, amplified, or synthetic) or RNA. Methods and algorithms for obtaining such polynucleotides are well known to those of skill in the art and can include, for example, methods for determining hybridization conditions which can routinely isolate polynucleotides ofthe desired sequence identities. A polynucleotide according to the invention can be joined to any of a variety of other nucleotide sequences by well-established recombinant DNA techniques (see Sambrook J et al. (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, NY). Useful nucleotide sequences for joining to polypeptides include an assortment of vectors, e.g., plasmids, cosmids, lambda phage derivatives, phagemids, and the like, that are well known in the art. Accordingly, the invention also provides a vector including a polynucleotide ofthe invention and a host cell containing the polynucleotide. In general, the vector contains an origin of replication functional in at least one organism, convenient restriction endonuclease sites, and a selectable marker for the host cell. Vectors according to the invention include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. A host cell according to the invention can be a prokaryotic or eukaryotic cell and can be a unicellular organism or part of a multicellular organism. The polynucleotides ofthe present invention also make possible the development, through, e.g., homologous recombination or knock out strategies, of animals that fail to express functional IL-lHyl or that express a variant of IL-lHyl. Such animals are useful as models for studying the in vivo activities of IL-lHyl as well as for studying modulators of IL-lHyl. In preferred methods to determine biological functions ofthe polypeptides of the invention in vivo, one or more genes provided by the invention are either over expressed or inactivated in the germ line of animals using homologous recombination [Capecchi, Science 244:1288-1292 (1989)]. Animals in which the gene is over expressed, under the regulatory control of exogenous or endogenous promoter elements, are known as transgenic animals. Animals in which an endogenous gene has been inactivated by homologous recombination are referred to as "knockout" animals. Knockout animals, preferably non-human mammals, can be prepared as described in U.S. Patent No. 5,557,032, incorporated herein by reference. Transgenic animals are useful to determine the roles polypeptides ofthe invention play in biological processes, and preferably in disease states. Transgenic animals are useful as model systems to identify compounds that modulate lipid metabolism. Transgenic animals, preferably non-human mammals, are produced using methods as described in U.S. Patent No 5,489,743 and PCT Publication No. WO94/28122, incoφorated herein by reference. Transgenic animals can be prepared wherein all or part of a polynucleotides of the invention promoter is either activated or inactivated to alter the level of expression ofthe polypeptides ofthe invention. Inactivation can be carried out using homologous recombination methods described above. Activation can be achieved by supplementing or even replacing the homologous promoter to provide for increased protein expression. The homologous promoter can be supplemented by insertion of one or more heterologous enhancer elements known to confer promoter activation in a particular tissue. Knowledge of IL-lHyl DNA sequences allows for modification of cells to permit, or increase, expression of endogenous IL-lHyl. Cells can be modified (e.g., by homologous recombination) to provide increased EL-lHyl expression by replacing, in whole or in part, the naturally occurring IL-lHyl promoter with all or part of a heterologous promoter so that the cells express IL-lHyl at higher levels. The heterologous promoter is inserted in such a manner that it is operatively linked to EL- lHyl encoding sequences. See, for example, PCT International Publication No. WO94/12650, PCT International Publication No. WO92/20808, and PCT International Publication No. WO91/09955. It is also contemplated that, in addition to heterologous promoter DNA, amplifiable marker DNA (e.g., ada, dhfr, and the multifunctional CAD gene which encodes carbamyl phosphate synthase, aspartate transcarbamylase, and dihydroorotase) and or intron DNA may be inserted along with the heterologous promoter DNA. If linked to the IL-lHyl coding sequence, amplification ofthe marker DNA by standard selection methods results in co-amplification ofthe IL-lHyl coding sequences in the cells. The sequences falling within the scope ofthe present invention are not limited to the specific sequences herein described, but also include allelic variations thereof. Allelic variations can be routinely determined by comparing the sequence provided in SEQ DD NOS: 1, 2, 4, 6, 7 or 8, a representative fragment thereof, or a nucleotide sequence at least 99.9% identical to SEQ DD NOS: 1, 2, 4, 6, 7, or 8, with a sequence from another isolate ofthe same species. Furthermore, to accommodate codon variability, the invention includes nucleic acid molecules coding for the same amino acid sequences as do the specific ORFs disclosed herein. In other words, in the coding region of an ORF, substitution of one codon for another which encodes the same amino acid is expressly contemplated. Any specific sequence disclosed herein can be readily screened for errors by resequencing a particular fragment, such as an ORF, in both directions (i.e., sequence both strands). The present invention further provides recombinant constructs comprising a nucleic acid having the sequence of SEQ DD NOS: 1, 2, 4, 6, 7 or 8, or a fragment thereof. The recombinant constructs ofthe present invention comprise a vector, such as a plasmid or viral vector, into which a nucleic acid having the sequence of SEQ DD NOS: 1, 2, 4, 6, 7 or 8 or a fragment thereof is inserted, in a forward or reverse orientation. In the case of a vector comprising one of the ORFs ofthe present invention, the vector may further comprise regulatory sequences, including for example, a promoter, operably linked to the ORF. For vectors comprising the EMFs and UMFs ofthe present invention, the vector may further comprise a marker sequence or heterologous ORF operably linked to the EMF or UMF. Large numbers of suitable vectors and promoters are known to those of skill in the art and are commercially available for generating the recombinant constructs ofthe present invention. The following vectors are provided by way of example. Bacterial: pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene); pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacia). Eukaryotic: pWLneo, pSV2cat, pOG44, PXTI, pSG (Stratagene) pSVK3, pBPV, pMSG, pSVL (Pharmacia). The isolated polynucleotide ofthe invention may be operably linked to an expression control sequence such as the pMT2 or pED expression vectors disclosed in Kaufman et al., Nucleic Acids Res. 19, 4485-4490 (1991), in order to produce the protein recombinantly. Many suitable expression control sequences are known in the art. General methods of expressing recombinant proteins are also known and are exemplified in R. Kaufman, Methods in Enzymology 185, 537-566 (1990). As defined herein "operably linked" means that the isolated polynucleotide ofthe invention and an expression control sequence are situated within a vector or cell in such a way that the protein is expressed by a host cell which has been transformed (transfected) with the ligated polynucleotide/expression control sequence. Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are pKK232-8 and pCM7. Particular named bacterial promoters include lad, lacZ, T3, T7, gpt, lambda P R , and tre. Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection ofthe appropriate vector and promoter is well within the level of ordinary skill in the art. Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the ampicillin resistance gene of E. coli and S. cerevisiae TRPl gene, and a promoter derived from a highly-expressed gene to direct transcription of a downstream structural sequence. Such promoters can be derived from operons encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), a-factor, acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein into the periplasmic space or extracellular medium. Optionally, the heterologous sequence can encode a fusion protein including an N-terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product. Useful expression vectors for bacterial use are constructed by inserting a structural DNA sequence encoding a desired protein together with suitable translation initiation and termination signals in operable reading phase with a functional promoter. The vector will comprise one or more phenotypic selectable markers and an origin of replication to ensure maintenance ofthe vector and to, if desirable, provide amplification within the host. Suitable prokaryotic hosts for transformation include E. coli, Bacillus subtilis, Salmonella typhimurium and various species within the genera Pseudomonas, Streptomyces, and Staphylococcus, although others may also be employed as a matter of choice. As a representative but non-limiting example, useful expression vectors for bacterial use can comprise a selectable marker and bacterial origin of replication derived from commercially available plasmids comprising genetic elements ofthe well known cloning vector pBR322 (ATCC 37017). Such commercial vectors include, for example, pKK223-3 (Pharmacia Fine Chemicals, Uppsala, Sweden) and GEM 1 (Promega Biotech, Madison, WI, USA). These pBR322 "backbone" sections are combined with an appropriate promoter and the structural sequence to be expressed. Following transformation of a suitable host strain and growth ofthe host strain to an appropriate cell density, the selected promoter is induced or derepressed by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period. Cells are typically harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification. Included within the scope ofthe nucleic acid sequences ofthe invention are nucleic acid sequences that hybridize under stringent conditions to a fragment ofthe DNA sequence in Figures 2, 5, 8, or 9 or its complement, which fragment is greater than about 10 bp, preferably 20-50 bp, and even greater than 100 bp. In accordance with the invention, polynucleotide sequences which encode the novel nucleic acids, or functional equivalents thereof, may be used to generate recombinant DNA molecules that direct the expression of that nucleic acid, or a functional equivalent thereof, in appropriate host cells. The nucleic acid sequences ofthe invention are further directed to sequences which encode variants ofthe described nucleic acids. These amino acid sequence variants may be prepared by methods known in the art by introducing appropriate nucleotide changes into a native or variant polynucleotide. There are two variables in the construction of amino acid sequence variants: the location ofthe mutation and the nature ofthe mutation. The amino acid sequence variants ofthe nucleic acids are preferably constructed by mutating the polynucleotide to give an amino acid sequence that does not occur in nature. These amino acid alterations can be made at sites that differ in the nucleic acids from different species (variable positions) or in highly conserved regions (constant regions). Sites at such locations will typically be modified in series, e.g., by substituting first with conservative choices (e.g., hydrophobic amino acid to a different hydrophobic amino acid) and then with more distant choices (e.g., hydrophobic amino acid to a charged amino acid), and then deletions or insertions may be made at the target site. Amino acid sequence deletions generally range from about 1 to 30 residues, preferably about 1 to 10 residues, and are typically contiguous. Amino acid insertions include amino- and/or carboxyl-terminal fusions ranging in length from one to one hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Intrasequence insertions may range generally from about 1 to 10 amino residues, preferably from 1 to 5 residues. Examples of terminal insertions include the heterologous signal sequences necessary for secretion or for intracellular targeting in different host cells. In a preferred method, polynucleotides encoding the novel nucleic acids are changed via site-directed mutagenesis. This method uses oligonucleotide sequences that encode the polynucleotide sequence ofthe desired amino acid variant, as well as a sufficient adjacent nucleotide on both sides ofthe changed amino acid to form a stable duplex on either side ofthe site of being changed. In general, the techniques of site-directed mutagenesis are well known to those of skill in the art and this technique is exemplified by publications such as, Edelman et al., DNA 2:183 (1983). A versatile and efficient method for producing site-specific changes in a polynucleotide sequence was published by Zoller and Smith, Nucleic Acids Res. 10:6487-6500 (1982). PCR may also be used to create amino acid sequence variants ofthe novel nucleic acids. When small amounts of template DNA are used as starting material, primer(s) that differs slightly in sequence from the corresponding region in the template DNA can generate the desired amino acid variant. PCR amplification results in a population of product DNA fragments that differ from the polynucleotide template encoding the polypeptide at the position specified by the primer. The product DNA fragments replace the corresponding region in the plasmid and this gives the desired amino acid variant. A further technique for generating amino acid variants is the cassette mutagenesis technique described in Wells et al., Gene 34:315 (1985); and other mutagenesis techniques well known in the art, such as, for example, the techniques in Sambrook et al., supra, and Current Protocols in Molecular Biology, Ausubel et al. Due to the inherent degeneracy ofthe genetic code, other DNA sequences which encode substantially the same or a functionally equivalent amino acid sequence may be used in the practice ofthe invention for the cloning and expression of these novel nucleic acids. Such DNA sequences include those which are capable of hybridizing to the appropriate novel nucleic acid sequence under stringent conditions. Polynucleotides ofthe invention can also be used to induce immune responses. For example, as described in Fan et al., Nat. Biotech. 17:870-872 (1999), incoφorated herein by reference, nucleic acid sequences encoding a polypeptide may be used to generate antibodies against the encoded polypeptide following topical administration of naked plasmid DNA or following injection, and preferably intramuscular injection ofthe DNA. The nucleic acid sequences are preferably inserted in a recombinant expression vector and may be in the form of naked DNA. 6.3. HOSTS The present invention further provides host cells genetically engineered to contain the polynucleotides ofthe invention. For example, such host cells may contain nucleic acids ofthe invention introduced into the host cell using known transformation, transfection or infection methods. The present invention still further provides host cells genetically engineered to express the polynucleotides ofthe invention, wherein such polynucleotides are in operative association with a regulatory sequence heterologous to the host cell which drives expression ofthe polynucleotides in the cell. The host cell can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic host cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Introduction of the recombinant construct into the host cell can be effected by calcium phosphate transfection, DEAE, dextran mediated transfection, or electroporation (Davis, L. et al., Basic Methods in Molecular Biology (1986)). The host cells containing one of polynucleotides ofthe invention, can be used in conventional manners to produce the gene product encoded by the isolated fragment (in the case of an ORF) or can be used to produce a heterologous protein under the control ofthe EMF. Any host/vector system can be used to express one or more ofthe ORFs of the present invention. These include, but are not limited to, eukaryotic hosts such as HeLa cells, Cv-1 cell, COS cells, and Sf9 cells, as well as prokaryotic host such as E. coli and B. subtilis. The most preferred cells are those which do not normally express the particular polypeptide or protein or which expresses the polypeptide or protein at low natural level. Mature proteins can be expressed in mammalian cells, yeast, bacteria, or other cells under the control of appropriate promoters. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described by Sambrook, et al., in Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor, New York (1989), the disclosure of which is hereby incoφorated by reference. Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described by Gluzman, Cell 23:175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell tines. Mammalian expression vectors will comprise an origin of replication, a suitable promoter and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5' flanking nontranscribed sequences. DNA sequences derived from the SV40 viral genome, for example, SV40 origin, early promoter, enhancer, splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements. Recombinant polypeptides and proteins produced in bacterial culture are usually isolated by initial extraction from cell pellets, followed by one or more salting-out, aqueous ion exchange or size exclusion chromatography steps. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed for final purification steps. Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents. A number of types of cells may act as suitable host cells for expression ofthe protein. Mammalian host cells include, for example, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Colo205 cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal diploid cells, cell strains derived from in vitro culture of primary tissue, primary explants, HeLa cells, mouse L cells, BHK, HL-60, U937, HaK or Jurkat cells. Alternatively, it may be possible to produce the protein in lower eukaryotes such as yeast or in prokaryotes such as bacteria. Potentially suitable yeast strains include Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains, Candida, or any yeast strain capable of expressing heterologous proteins. Potentially suitable bacterial strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium, or any bacterial strain capable of expressing heterologous proteins. If the protein is made in yeast or bacteria, it may be necessary to modify the protein produced therein, for example by phosphorylation or glycosylation ofthe appropriate sites, in order to obtain the functional protein. Such covalent attachments may be accomplished using known chemical or enzymatic methods. In another embodiment ofthe present invention, cells and tissues may be engineered to express an endogenous gene comprising the polynucleotides ofthe invention under the control of inducible regulatory elements, in which case the regulatory sequences ofthe endogenous gene may be replaced by homologous recombination. As described herein, gene targeting can be used to replace a gene's existing regulatory region with a regulatory sequence isolated from a different gene or a novel regulatory sequence synthesized by genetic engineering methods. Such regulatory sequences may be comprised of promoters, enhancers, scaffold-attachment regions, negative regulatory elements, transcriptional initiation sites, regulatory protein binding sites or combinations of said sequences. Alternatively, sequences which affect the structure or stability ofthe RNA or protein produced may be replaced, removed, added, or otherwise modified by targeting, including polyadenylation signals. mRNA stability elements, splice sites, leader sequences for enhancing or modifying transport or secretion properties of the protein, or other sequences which alter or improve the function or stability of protein or RNA molecules. The targeting event may be a simple insertion ofthe regulatory sequence, placing the gene under the control ofthe new regulatory sequence, e.g., inserting a new promoter or enhancer or both upstream of a gene. Alternatively, the targeting event may be a simple deletion of a regulatory element, such as the deletion of a tissue-specific negative regulatory element. Alternatively, the targeting event may replace an existing element; for example, a tissue-specific enhancer can be replaced by an enhancer that has broader or different cell-type specificity than the naturally occurring elements. Here, the naturally occurring sequences are deleted and new sequences are added. In all cases, the identification of the targeting event may be facilitated by the use of one or more selectable marker genes that are contiguous with the targeting DNA, allowing for the selection of cells in which the exogenous DNA has integrated into the host cell genome. The identification ofthe targeting event may also be facilitated by the use of one or more marker genes exhibiting the property of negative selection, such that the negatively selectable marker is linked to the exogenous DNA, but configured such that the negatively selectable marker flanks the targeting sequence, and such that a correct homologous recombination event with sequences in the host cell genome does not result in the stable integration ofthe negatively selectable marker. Markers useful for this puφose include the Heφes Simplex Virus thymidine kinase (TK) gene or the bacterial xanthine-guanine phosphoribosyl-transferase (gpt) gene. The gene targeting or gene activation techniques which can be used in accordance with this aspect ofthe invention are more particularly described in U.S. Patent No. 5,272,071 to Chappel; U.S. Patent No. 5,578,461 to Sherwin et al.; International Application No. PCT/US92/09627 (WO93/09222) by Selden et al.; and International Application No. PCT/US 90/06436 (WO91/06667) by Skoultchi et al., each of which is incoφorated by reference herein in its entirety. 6.4. POLYPEPTIDES OF THE INVENTION SEQ DD NO: 2 encodes the polypeptide sequence of SEQ DD NO: 3. An amino acid alignment of SEQ DD NO: 3 and rat, mouse, rabbit and human Interleukin-1 receptor antagonist polypeptides is shown Fig. 1. SEQ DD NO: 3 displays significant (71%) amino acid homology with human Interleukin-1 receptor antagonist, and thus, represents a novel molecule that is highly related to, yet distinct from Interleukin-1 receptor antagonist. This is the first cloned sequence of an Interleukin-1 receptor antagonist related gene. This discovery of SEQ DD NO: 3 indicates that a family of Interleukin-1 receptor antagonist related genes exists. Additional family members can be identified using SEQ DD NO: 1 or 2 as a molecular probe. SEQ DD NO: 3 encodes a protein that contains a 4 amino acid insertion differing from all other previously characterized Interleukin-1 receptor antagonists sequences (Figure 1). This insertion may provide SEQ DD NO: 3 with a novel and previously uncharacterized activity. Likewise, Figure 7 presents an amino acid alignment of SEQ DD NO: 5 with the cytoplasmic form of human IL-1 Ra (labeled ΗUMILIRASIC"). The alignment reveals a high degree of homology between the two; 48% ofthe amino acids were identical and 54% represent conservative amino acid substitutions. Interleukin-1 has pleiotropic biological activities many of which adversely affect the organism, it would be expected that the molecule must be tightly regulated if it is not to be injurious. Indeed, there are several reports of Interleukin-1 inhibitors that regulate the action of Interleukin-1. Interleukin-1 inhibitory activity has been reported in monocyte conditioned medium, wherein the monocytes are grown on adherent immune complexes. Arena, W. P., et al., 1985, Journal of Immun., 134:3868. Additionally, an inhibitor has been reported to be present urine. Seckinger, P., et al., 1987, Journal of Immun., 139:1546. Lastly, a protein inhibitor, purified and cloned, that has interleukin-1 receptor antagonist activity has been reported. Hannum, et at., 1990, Nature, 343:336, and Eisenberg, S., et al., 1990, Nature, 343:341. It is thought that the Interleukin-1 inhibitor present in urine, and which has been partially purified and characterized by Seckinger, P. et al., and Seckinger, P., et al., 1987, Journal of Immun., 139:1541 is similar, if not identical to the cloned Interleukin-1 receptor antagonist reported by Eisenberg, S., et al. (1990), Nature, 343:341 ; and Carter, D., et al (1990), Nature, 344:633. Interleukin-1 receptor antagonist is a naturally occurring peptide secreted by macrophages in response to many of the same stimuli which cause the secretion of Interleukin-1 itself. Interleukin-1 receptor antagonist is a naturally occurring antagonist to the cytokines and recognizes receptors on various cell types and blocks Interleukin-1 mediated responses by occupying the receptor. (Wakabayashi et al., FASEB J 1991;5:338; Okusawa et al. J Clin Invest 1988;81 :1162; Ohlsson et al., Nature 1990;348:550; Aiura, et al. Cytokine 1991 ;4:498; Fischer et al. Am J Physiol 1991 ;261 :R442). In humans, Interleukin-1 receptor antagonist is a naturally occurring group of molecules; three forms have been characterized (two glycosylated and one non-glycosylated). Fischer et al. (Am J Physiol 1991;261:R442) demonstrated that the administration of a naturally occurring antagonist to Interleukin-1 will significantly blunt the cytokine cascade and improve survival in baboons given a lethal dose of live bacteria. Interleukin-1 receptor antagonist significantly attenuates the decrease in mean arterial pressure and cardiac output and improves survival for severe acute pancreatitis. (U.S. Pat. NO. 5 ,508,262) The systemic Interleukin-1 response observed as a result of bacterial sepsis was also diminished significantly, correlating with a decrease in the systemic response to bacterial sepsis. Studies by Aiura et al. 9 Cytokine 1991;4:498) have shown that Interleukin-1 receptor antagonist is protective in a rabbit model of hypotensive gram-positive septic shock. The administration of Interleukin-1 receptor antagonist in this animal model has been shown to maintain mean arterial pressure compared to control, as well as decreasing lung water and maintaining urine output. This work demonstrated the role of Interleukin-1 and the protective role of Interleukin-1 receptor antagonist in gram-positive septic shock. Interleukin-1 is the principal mediator in a patient's clinical response to multiple different stresses regardless ofthe etiology (including acute pancreatitis, sepsis, endotoxin shock, and cytokine induced shock). The isolated polypeptides ofthe invention include, but are not limited to, a polypeptide comprising the amino acid sequence of SEQ DD NOS: 3 or 5; a full length protein coding sequence of SEQ DD NOS: 3 or 5; a mature protein coding sequence of SEQ ID NOS: 3 or 5, or ; a polypeptide encoded by one or more ofthe exons of SEQ DD NOS: 7 or 8. The polypeptides ofthe present invention further include, but are not limited to, a polypeptide comprising the amino acid sequence encoded by the cDNA insert of clone pEL-lHy273 deposited with the American Type Culture Collection (ATCC; 10801 University Blvd., Manassas, Virginia, 20110-2209, U.S.A.); a full length protein of SEQ DD NO: 3 or 5 assembled from the amino acid sequence encoded by the cDNA insert of clone pIL-lHy273; or, a mature protein coding sequence of SEQ DD NO: 3 or 5 assembled from the amino acid sequence encoded by cDNA insert of clone pIL-lHy273. Protein compositions ofthe present invention may further comprise an acceptable carrier, such as a hydrophilic, e.g., pharmaceutically acceptable, carrier. The invention also relates to methods for producing a polypeptide comprising growing a culture ofthe cells ofthe invention in a suitable culture medium, and purifying the protein from the culture. For example, the methods ofthe invention include a process for producing a polypeptide in which a host cell containing a suitable expression vector that includes a polynucleotide ofthe invention is cultured under conditions that allow expression ofthe encoded polypeptide. The polypeptide can be recovered from the culture, conveniently from the culture medium, and further purified. Preferred embodiments include those in which the protein produced by such process is a full length or mature form ofthe protein. The invention further provides a polypeptide including an amino acid sequence that is substantially equivalent to SEQ DD NOS: 3 or 5. Polypeptides according to the invention can have at least about 95%, and more typically at least about 98%, sequence identity to SEQ DD NOS: 3 or 5. The present invention further provides isolated polypeptides encoded by the nucleic acid fragments ofthe present invention or by degenerate variants ofthe nucleic acid fragments ofthe present invention. By "degenerate variant" is intended nucleotide fragments which differ from a nucleic acid fragment ofthe present invention (e.g., an ORF) by nucleotide sequence but, due to the degeneracy ofthe genetic code, encode an identical polypeptide sequence. Preferred nucleic acid fragments ofthe present invention are the ORFs that encode proteins. A variety of methodologies known in the art can be utilized to obtain any one ofthe isolated polypeptides or proteins ofthe present invention. At the simplest level, the amino acid sequence can be synthesized using commercially available peptide synthesizers. This is particularly useful in producing small peptides and fragments of larger polypeptides. Fragments are useful, for example, in generating antibodies against the native polypeptide. In an alternative method, the polypeptide or protein is purified from bacterial cells which naturally produce the polypeptide or protein. One skilled in the art can readily follow known methods for isolating polypeptides and proteins in order to obtain one ofthe isolated polypeptides or proteins ofthe present invention. These include, but are not limited to, immunochromatography, HPLC, size-exclusion chromatography, ion-exchange chromatography, and immuno-affinity chromatography. See, e.g., Scopes, Protein Purification: Principles and Practice, Springer-Verlag (1994); Sambrook, et al., in Molecular Cloning: A Laboratory Manual; Ausubel et al., Current Protocols in Molecular Biology. The polypeptides and proteins ofthe present invention can alternatively be purified from cells which have been altered to express the desired polypeptide or protein. As used herein, a cell is said to be altered to express a desired polypeptide or protein when the cell, through genetic manipulation, is made to produce a polypeptide or protein which it normally does not produce or which the cell normally produces at a lower level. One skilled in the art can readily adapt procedures for introducing and expressing either recombinant or synthetic sequences into eukaryotic or prokaryotic cells in order to generate a cell which produces one ofthe polypeptides or proteins of the present invention. The purified polypeptides can be used in in vitro binding assays which are well known in the art to identify molecules which bind to the polypeptides. These molecules include but are not limited to, for e.g., small molecules, molecules from combinatorial libraries, antibodies or other proteins. The molecules identified in the binding assay are then tested for antagonist or agonist activity in in vivo tissue culture or animal models that are well known in the art. In brief, the molecules are titrated into a plurality of cell cultures or animals and then tested for either cell/animal death or prolonged survival ofthe animal/cells. In addition, the binding molecules may be complexed with toxins, e.g., ricin or cholera, or with other compounds that are toxic to cells. The toxin-binding molecule complex is then targeted to a tumor or other cell by the specificity of the binding molecule for SEQ DD NO: 3 or 5. The protein ofthe invention may also be expressed as a product of transgenic animals, e.g., as a component ofthe milk of transgenic cows, goats, pigs, or sheep which are characterized by somatic or germ cells containing a nucleotide sequence encoding the protein. The protein may also be produced by known conventional chemical synthesis. Methods for constructing the proteins ofthe present invention by synthetic means are known to those skilled in the art. The synthetically constructed protein sequences, by virtue of sharing primary, secondary or tertiary structural and/or conformational characteristics with proteins may possess biological properties in common therewith, including protein activity. Thus, they may be employed as biologically active or immunological substitutes for natural, purified proteins in screening of therapeutic compounds and in immunological processes for the development of antibodies. The proteins provided herein also include proteins characterized by amino acid sequences similar to those of purified proteins but into which modification are naturally provided or deliberately engineered. For example, modifications in the peptide or DNA sequences can be made by those skilled in the art using known techniques. Modifications of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence. For example, one or more ofthe cysteine residues may be deleted or replaced with another amino acid to alter the conformation ofthe molecule. Techniques for such alteration, substitution, replacement, insertion or deletion are well known to those skilled in the art (see, e.g., U.S. Pat. No. 4,518,584). Preferably, such alteration, substitution, replacement, insertion or deletion retains the desired activity ofthe protein. Other fragments and derivatives ofthe sequences of proteins which would be expected to retain protein activity in whole or in part and may thus be useful for screening or other immunological methodologies may also be easily made by those skilled in the art given the disclosures herein. Such modifications are believed to be encompassed by the present invention. The protein may also be produced by operably linking the isolated polynucleotide ofthe invention to suitable control sequences in one or more insect expression vectors, and employing an insect expression system. Materials and methods for baculovirus/insect cell expression systems are commercially available in kit form from, e.g., Invitrogen, San Diego, Calif, U.S.A. (the MaxBat.RTM. kit), and such methods are well known in the art, as described in Summers and Smith, Texas Agricultural Experiment Station Bulletin No. 1555 (1987), incoφorated herein by reference. As used herein, an insect cell capable of expressing a polynucleotide ofthe present invention is "transformed." The protein of the invention may be prepared by culturing transformed host cells under culture conditions suitable to express the recombinant protein. The resulting expressed protein may then be purified from such culture (i.e., from culture medium or cell extracts) using known purification processes, such as gel filtration and ion exchange chromatography. The purification ofthe protein may also include an affinity column containing agents which will bind to the protein; one or more column steps over such affinity resins as concanavalin A-agarose, heparin-toyopearl.RTM. or Cibacrom blue 3GA Sepharose.RTM.; one or more steps involving hydrophobic interaction chromatography using such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffinity chromatography. Alternatively, the protein ofthe invention may also be expressed in a foπn which will facilitate purification. For example, it may be expressed as a fusion protein, such as those of maltose binding protein (MBP), glutathione-S-transferase (GST) or thioredoxin (TRX). Kits for expression and purification of such fusion proteins are commercially available from New England BioLab (Beverly, Mass.), Pharmacia (Piscataway, N.J.) and In Vitrogen, respectively. The protein can also be tagged with an epitope and subsequently purified by using a specific antibody directed to such epitope. One such epitope ("Flag") is commercially available from Kodak (New Haven, Conn.). Finally, one or more reverse-phase high performance liquid chromatography (RP-HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further purify the protein. Some or all ofthe foregoing purification steps, in various combinations, can also be employed to provide a substantially homogeneous isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined in accordance with the present invention as an "isolated protein." The polypeptides ofthe invention include Interleukin-1 Receptor Antagonist (IL-1 RA) analogs. This embraces fragments of EL-1 RA ofthe invention, as well as Interleukin-1 Receptor Antagonists which comprise one or more amino acids deleted, inserted, or substituted. Also, analogs of Interleukin-1 Receptor Antagonist ofthe invention embrace fusions of Interleukin-1 Receptor Antagonist or modifications of Interleukin-1 Receptor Antagonist, wherein the Interleukin-1 Receptor Antagonist or analog is fused to another moiety or moieties, e.g., targeting moiety or another therapeutic agent. Such analogs may exhibit improved properties such as activity and/or stability. Examples of moieties which may be fused to Interleukin-1 Receptor Antagonist or an analog include, for example, targeting moieties which provide for the delivery of polypeptide to pancreatic cells, e.g., antibodies to pancreatic cells, antibodies to immune cells such as T-cells, monocytes, dendritic cells, granulocytes, etc., as well as receptor and ligands expressed on pancreatic or immune cells. Other moieties which may be fused to Interleukin-1 Receptor Antagonist include therapeutic agents which are used for treatment, for example, immunosuppressive drugs such as cyclosporin, SK506, azathioprine, CD3 antibodies and steroids. Also, Interleukin-1 Receptor Antagonist may be fused to immunostimulants, immune modulators, and other cytokines such as alpha or beta interferon. 6.5 GENE THERAPY Mutations in the IL-lHyl gene that result in loss of normal function ofthe IL- lHyl gene product underlie IL-lHyl -related human disease states. The invention comprehends gene therapy to restore normal IL-lHyl activity or to treating those disease states involving IL-lHyl. Delivery of a functional IL-lHyl gene to appropriate cells is effected ex vivo, in situ, or in vivo by use of vectors, and more particularly viral vectors (e.g., adenovirus, adeno-associated virus, or a retrovirus), or ex vivo by use of physical DNA transfer methods (e.g., liposomes or chemical treatments). See, for example, Anderson, Nature, supplement to vol. 392, no 6679, pp. 25-30 (1998). For additional reviews of gene therapy technology, see Friedmann, Science, 244: 1275-1281 (1989); Verma, Scientific American: 68-84 (1990); and Miller, Nature, 357: 455-460 (1992). Introduction of any one of the nucleotides of the present invention or a gene encoding the polypeptides ofthe present invention can also be accomplished with extrachromosomal substrates (transient expression) or artificial chromosomes (stable expression). Cells may also be cultured ex vivo in the presence of proteins ofthe present invention in order to proliferate or to produce a desired effect on or activity in such cells. Treated cells can then be introduced in vivo for therapeutic puφoses. Alternatively, it is contemplated that in other human disease states, preventing the expression of or inhibiting the activity of IL-lHyl will be useful in treating the disease states. It is contemplated that antisense therapy or gene therapy could be applied to negatively regulate the expression of polypeptides ofthe invention. Other methods inhibiting expression of a protein include the introduction of antisense molecules to the nucleic acids ofthe present invention, their complements, or their translated RNA sequences, by methods known in the art, the removal ofthe nucleic acids ofthe present invention such as using targeted deletion methods, or the insertion of a negative regulatory element such as a silencer, which is tissue specific. Further, the polypeptides ofthe present invention can be inhibited by the introduction of antisense molecules that hybridize to nucleic acids that encode for the polypeptides of the present invention and by the removal of a gene that encode for the polypeptides of the present invention. The present invention still further provides cells genetically engineered in vivo to express the polynucleotides ofthe invention, wherein such polynucleotides are in operative association with a regulatory sequence heterologous to the host cell which drives expression ofthe polynucleotides in the cell. These methods can be used to increase or decrease the expression of the polynucleotides ofthe present invention. Knowledge of DNA sequences provided by the invention allows for modification of cells to permit, increase, or decrease, expression of endogenous polypeptide. Cells can be modified (e.g., by homologous recombination) to provide increased polypeptide expression by replacing, in whole or in part, the naturally occurring promoter with all or part of a heterologous promoter so that the cells express the protein at higher levels. The heterologous promoter is inserted in such a manner that it is operatively linked to the desired protein encoding sequences. See, for example, PCT International Publication No. WO 94/12650, PCT International Publication No. WO 92/20808, and PCT International Publication No. WO 91/09955. It is also contemplated that, in addition to heterologous promoter DNA, amplifiable marker DNA (e.g., ada, dhfr, and the multifunctional CAD gene which encodes carbamyl phosphate synthase, aspartate transcarbamylase, and dihydroorotase) and/or intron DNA may be inserted along with the heterologous promoter DNA. If linked to the desired protein coding sequence, amplification ofthe marker DNA by standard selection methods results in co-amplification ofthe desired protein coding sequences in the cells. In another embodiment ofthe present invention, cells and tissues may be engineered to express an endogenous gene comprising the polynucleotides ofthe invention under the control of inducible regulatory elements, in which case the regulatory sequences ofthe endogenous gene may be replaced by homologous recombination. As described herein, gene targeting can be used to replace a gene's existing regulatory region with a regulatory sequence isolated from a different gene or a novel regulatory sequence synthesized by genetic engineering methods. Such regulatory sequences may be comprised of promoters, enhancers, scaffold-attachment regions, negative regulatory elements, transcriptional initiation sites, regulatory protein binding sites or combinations of said sequences. Alternatively, sequences which affect the structure or stability ofthe RNA or protein produced may be replaced, removed, added, or otherwise modified by targeting. These sequence include polyadenylation signals, mRNA stability elements, splice sites, leader sequences for enhancing or modifying transport or secretion properties ofthe protein, or other sequences which alter or improve the function or stability of protein or RNA molecules. The targeting event may be a simple insertion ofthe regulatory sequence, placing the gene under the control ofthe new regulatory sequence, e.g., inserting a new promoter or enhancer or both upstream of a gene. Alternatively, the targeting event may be a simple deletion of a regulatory element, such as the deletion of a tissue-specific negative regulatory element. Alternatively, the targeting event may replace an existing element; for example, a tissue-specific enhancer can be replaced by an enhancer that has broader or different cell-type specificity than the naturally occurring elements. Here, the naturally occurring sequences are deleted and new sequences are added. In all cases, the identification ofthe targeting event may be facilitated by the use of one or more selectable marker genes that are contiguous with the targeting DNA, allowing for the selection of cells in which the exogenous DNA has integrated into the cell genome. The identification ofthe targeting event may also be facilitated by the use of one or more marker genes exhibiting the property of negative selection, such that the negatively selectable marker is linked to the exogenous DNA, but configured such that the negatively selectable marker flanks the targeting sequence, and such that a correct homologous recombination event with sequences in the host cell genome does not result in the stable integration ofthe negatively selectable marker. Markers useful for this puφose include the Heφes Simplex Virus thymidine kinase (TK) gene or the bacterial xanthine-guanine phosphoribosyl-transferase (gpt) gene. The gene targeting or gene activation techniques which can be used in accordance with this aspect ofthe invention are more particularly described in U.S. Patent No. 5,272,071 to Chappel; U.S. Patent No. 5,578,461 to Sherwin et al.; International Application No. PCT/US92/09627 (WO93/09222) by Selden et al.; and International Application No. PCT/US90/06436 (WO91/06667) by Skoultchi et al., each of which is incoφorated by reference herein in its entirety. 6.6. DEPOSIT OF CLONE The following clone, pIL-lHy 273 was deposited with the American Type Culture Collection (ATCC) 10801 University Avenue, Manassas, Virginia, on March 12, 1999 under the terms ofthe Budapest Treaty. The 2,648 base pair cDNA insert of clone pIL-lHy 273 is contained in vector pSPORTl and is flanked by Notl and Sail restriction sites. The clone represent a plasmid clone as described in the Examples set forth below. Microorganism/Clone ATCC Accession No. pIL-lHy 273 203841 6.7. USES AND BIOLOGICAL ACTIVITY The polynucleotides and proteins ofthe present invention are expected to exhibit one or more ofthe uses or biological activities (including those associated with assays cited herein) identified below. Uses or activities described for proteins ofthe present invention may be provided by administration or use of such proteins or by administration or use of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA). 6.7.1. RESEARCH USES AND UTILITIES The polynucleotides provided by the present invention can be used by the research community for various puφoses. The polynucleotides can be used to express recombinant protein for analysis, characterization or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on Southern gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fingeφrinting; as a probe to "subtract-out" known sequences in the process of discovering other novel polynucleotides; for selecting and making oligomers for attachment to a "gene chip" or other support, including for examination of expression patterns; to raise anti-protein antibodies using DNA immunization techniques; and as an antigen to raise anti-DNA antibodies or elicit another immune response. Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the polynucleotide can also be used in interaction trap assays (such as, for example, that described in Gyuris et al., Cell 75:791-803 (1993)) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors ofthe binding interaction. The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels ofthe protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands. Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors ofthe binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists ofthe binding interaction. Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products. Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E. F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Berger, S. L. and A. R. Kimmel eds., 1987. 6.7.2. NUTRITIONAL USES Polynucleotides and proteins ofthe present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate. In such cases the protein or polynucleotide ofthe invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the protein or polynucleotide ofthe invention can be added to the medium in or on which the microorganism is cultured. 6.7.3. CYTOKINE AND CELL PROLIFERATION/DIFFERENTIATION ACTIVITY A protein ofthe present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. A polynucleotide ofthe invention can encode a polypeptide exhibiting such attributes. Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor-dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of a protein ofthe present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/11, BaF3, MC9/G, M+(preB M+), 2E8, RB5, DAI, 123, Tl 165, HT2, CTLL2, TF-1, Mo7e and CMK. The activity of a protein ofthe invention may, among other means, be measured by the following methods: Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Bertagnolli et al., J. Immunol. 145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Bertagnolli, et al., I. Immunol. 149:3778-3783, 1992; Bowman et al., I. Immunol. 152:1756-1761, 1994. Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in: Polyclonal T cell stimulation, Kruisbeek, A. M. and Shevach, E. M. In Current Protocols in immunology. J. E. e.a. Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and Measurement of mouse and human interleukin .gamma., Schreiber, R. D. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.8.1-6.8.8, John Wiley and Sons, Toronto. 1994. Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine Interleukin 2 and interleukin 4, Bottomly, K., Davis, L. S. and Lipsky, P. E. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211 , 1991; Moreau et al., Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-2938, 1983; Measurement of mouse and human interleukin 6— Nordan, R. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991 ; Smith et al., Proc. Natl. Aced. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human Interleukin 11— Bennett, F., Giannotti, J., Clark, S. C. and Turner, K. J. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.15.1 John Wiley and Sons, Toronto. 1991; Measurement of mouse and human interleukin 9— Ciarletta, A., Giannotti, J., Clark, S. C. and Turner, K. J. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto. 1991. Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al., Eur. J. Immun. 11 :405-411, 1981 ; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988. 6.7.4. IMMUNE STIMULATING OR SUPPRESSING ACTIVITY A protein ofthe present invention may also exhibit immune stimulating or immune suppressing activity, including without limitation the activities for which assays are described herein. A polynucleotide ofthe invention can encode a polypeptide exhibiting such activities. A protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SCDD)), e.g., in regulating (up or down) growth and proliferation of T and/or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations. These immune deficiencies may be genetic or be caused by viral (e.g., HIV) as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein ofthe present invention, including infections by HIV, hepatitis viruses, heφes viruses, mycobacteria, Leishmania spp., malaria spp. and various fungal infections such as candidiasis. Of course, in this regard, proteins ofthe present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer. IL-1 has been indicated to promote tumor cell growth in cancers of various organs including breast adenocarcinoma, brain tumors, melanoma, myeloma, giant cell tumors of bone, acute myelogenous leukemia, oral epidermoid carcinoma and squamous cell carcinoma; thus, treatment of such cancer disease states involving elevated levels of IL-1 with IL-1 Hyl polypeptides ofthe present invention is expected to ameliorate signs and symptoms of cancer. Autoimmune disorders which maybe treated using a protein ofthe present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease. Such a protein (or antagonists thereof, including antibodies) ofthe present invention may also to be useful in the treatment of allergic reactions and conditions (e.g., anaphylaxis, serum sickness, drug reactions, food allergies, insect venom allergies, mastocytosis, allergic rhinitis, hypersensitivity pneumonitis, urticaria, angioedema, eczema, atopic dermatitis, allergic contact dermatitis, erythema multiforme, Stevens- Johnson syndrome, allergic conjunctivitis, atopic keratoconjunctivitis, venereal keratoconjunctivitis, giant papillary conjunctivitis and contact allergies), such as asthma (particularly allergic asthma) or bronchitis (including chronic bronchitis) and other respiratory problems. Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein (or antagonists thereof) ofthe present invention. The therapeutic effects of IL-1 Hyl polypeptides or antagonists thereof on allergic reactions can be evaluated by in vivo animals models such as the cumulative contact enhancement test (Lastbom et al., Toxicology 125: 59-66, 1998), skin prick test (Hoffmann et al., Allergy 54: 446-54, 1999), guinea pig skin sensitization test (Vohr et al., Arch. Toxocol. 73: 501-9), and murine local lymph node assay (Kimber et al., J. Toxicol. Environ. Health 53: 563-79). Using the proteins ofthe invention it may also be possible to modulate immune responses, in a number of ways. Down regulation may be in the form of inhibiting or blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T cells may be inhibited by suppressing T cell responses or by inducing specific tolerance in T cells, or both, immunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure ofthe T cells to the suppressive agent. Tolerance, which involves inducing non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased. Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the absence ofthe tolerizing agent. Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as, for example, B7)), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD). For example, blockage of T cell function should result in reduced tissue destruction in tissue transplantation. Typically, in tissue transplants, rejection ofthe transplant is initiated through its recognition as foreign by T cells, followed by an immune reaction that destroys the transplant. The administration of a therapeutic composition ofthe invention may prevent cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant. Moreover, a lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen-blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens. The efficacy of particular therapeutic compositions in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al., Science 257:789-792 (1992) and Turka et al., Proc. Natl. Acad. Sci USA, 89: 11102-11105 (1992). In addition, murine models of GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of therapeutic compositions ofthe invention on the development of that disease. Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology ofthe diseases. Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms. Administration of reagents which block stimulation of T cells can be used to inhibit T cell activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen-specific tolerance of autoreactive T cells which could lead to long-term relief from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of human autoimmune diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/lpr/lpr mice or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB rats, and murine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 840-856). Upregulation of an antigen function (e.g., a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy. Upregulation of immune responses may be in the form of enhancing an existing immune response or eliciting an initial immune response. For example, enhancing an immune response may be useful in cases of viral infection, including systemic viral diseases such as influenza, the common cold, and encephalitis. Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen-pulsed APCs either expressing a peptide ofthe present invention or together with a stimulatory form of a soluble peptide ofthe present invention and reintroducing the in vitro activated T cells into the patient. Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein ofthe present invention as described herein such that the cells express all or a portion ofthe protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a costimulatory signal to, and thereby activate, T cells in vivo. A peptide of the present invention may provide the necessary stimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells. In addition, tumor cells which lack MHC class I or MHC class D molecules, or which fail to reexpress sufficient mounts of MHC class I or MHC class D molecules, can be transfected with nucleic acid encoding all or a portion of (e.g., a cytoplasmic-domain truncated portion) of an MHC class I .alpha, chain protein and .beta.. sub.2 microglobulin protein or an MHC class II .alpha, chain protein and an MHC class D .beta, chain protein to thereby express MHC class I or MHC class II proteins on the cell surface. Expression ofthe appropriate class I or class II MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e.g., B7-1 , B7-2, B7-3) induces a T cell mediated immune response against the transfected tumor cell. Optionally, a gene encoding an antisense construct which blocks expression of an MHC class II associated protein, such as the invariant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject. The activity of a protein ofthe invention may, among other means, be measured by the following methods: Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Cuπent Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, immunologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. Immunol. 135:1564-1572, 1985; Takai et al., I. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Bowmanet al., J. Virology 61 :1992-1998; Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., Cellular immunology 133:327-341, 1991; Brown et al., J. immunol. 153:3079-3092, 1994. Assays for T-cell-dependent immunoglobulin responses and isotype switching (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Thl/Th2 profiles) include, without limitation, those described in: Maliszewski, J. Immunol. 144:3028-3033, 1990; and Assays for B cell function: In vitro antibody production, Mond, J. J. and Brunswick, M. In Cuπent Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto. 1994. Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without limitation, those described in: Cuπent Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., J. Immunol. 149:3778-3783, 1992. Dendritic cell-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., Journal of Immunology 154:5071-5079, 1995; Porgador et al., Journal of Experimental Medicine 182:255-260, 1995; Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264, 1989; Bhardwaj et al., Journal of Clinical Investigation 94:797-807, 1994; and Inaba et al., Journal of Experimental Medicine 172:631-640, 1990. Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in: Darzynkiewicz et al., Cytometry 13:795-808, 1992; Gorczyca et al., Leukemia 7:659-670, 1993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991; Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993; Gorczyca et al., International Journal of Oncology 1 :639-648, 1992. Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122, 1994; Galy et al., Blood 85:2770-2778, 1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551, 1991. 6.7.5. HEMATOPOIESIS REGULATING ACTIVITY A protein ofthe present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies. Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemias or for use in conjunction with iπadiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid cells; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferation of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all ofthe above-mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post iπadiation/chemotherapy, either in-vivo or ex -vivo (i.e., in conjunction with bone maπow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal cells or genetically manipulated for gene therapy. The activity of a protein ofthe invention may, among other means, be measured by the following methods: Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above. Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. Cellular Biology 15:141-151, 1995; Keller et al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81 :2903-2915, 1993. Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate lympho-hematopoiesis) include, without limitation, those described in: Methylcellulose colony forming assays, Freshney, M. G. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, N.Y. 1994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992; Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, I. K. and Briddell, R. A. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 23-39, Wiley-Liss, Inc., New York, N.Y. 1994; Neben et al., Experimental Hematology 22:353-359, 1994; Cobblestone area forming cell assay, Ploemacher, R. E. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc., New York, N.Y. 1994; Long term bone maπow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New York, N.Y. 1994; Long term culture initiating cell assay, Sutherland, H. J. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 139-162, Wiley-Liss, Inc., New York, N.Y. 1994. 6.7.6. TISSUE GROWTH ACTIVITY A protein ofthe present invention also may have utility in compositions used for bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration, as well as for wound healing and tissue repair and replacement, and in the treatment of burns, incisions and ulcers. A protein ofthe present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals. Such a preparation employing a protein ofthe invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De novo bone formation induced by an osteogenic agent contributes to the repair of congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery. A protein of this invention may also be used in the treatment of periodontal disease, and in other tooth repair processes. Such agents may provide an environment to attract bone-forming cells, stimulate growth of bone-forming cells or induce differentiation of progenitors of bone- forming cells. A protein ofthe invention may also be useful in the treatment of osteoporosis or osteoarthritis, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes. Another category of tissue regeneration activity that may be attributable to the protein ofthe present invention is tendon/ligament formation. A protein ofthe present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition ofthe present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions ofthe present invention may provide environment to attract tendon- or ligament- forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions ofthe invention may also be useful in the treatment of tendinitis, caφal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art. The protein ofthe present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve tissue. More specifically, a protein may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the present invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a protein ofthe invention. Proteins ofthe invention may also be useful to promote better or faster closure of non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like. It is expected that a protein ofthe present invention may also exhibit activity for generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part ofthe desired effects may be by inhibition or modulation of fibrotic scarring to allow normal tissue to regenerate. A protein ofthe invention may also exhibit angiogenic activity. A protein ofthe present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage. A protein ofthe present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or cells; or for inhibiting the growth of tissues described above. The activity of a protein ofthe invention may, among other means, be measured by the following methods: Assays for tissue generation activity include, without limitation, those described in: International Patent Publication No. WO95/16035 (bone, cartilage, tendon); International Patent Publication No. WO95/05846 (nerve, neuronal); International Patent Publication No. WO91/07491 (skin, endothelium). Assays for wound healing activity include, without limitation, those described in: Winter, Epidermal Wound Healing, pps. 71-112 (Maibach, H. I. and Rovee, D. T., eds.), Year Book Medical Publishers, Inc., Chicago, as modified by Eaglstein and Mertz, J. Invest. Dermatol 71:382-84 (1978). 6.7.7. ACTIVIN/INHIBIN ACTIVITY A protein ofthe present invention may also exhibit activin- or inhibin-related activities. A polynucleotide ofthe invention may encode a polypeptide exhibiting such characteristics. Inhibins are characterized by their ability to inhibit the release of follicle stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a protein ofthe present invention, alone or in heterodimers with a member ofthe inhibin α-family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts of other inhibins can induce infertility in these mammals. Alternatively, the protein ofthe invention, as a homodimer or as a heterodimer with other protein subunits ofthe inhibin-β group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells ofthe anterior pituitary. See, for example, U.S. Pat. No. 4,798,885. A protein ofthe invention may also be useful for advancement ofthe onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs. The activity of a protein ofthe invention may, among other means, be measured by the following methods: Assays for activin/inhibin activity include, without limitation, those described in: Vale et al., Endocrinology 91:562-572, 1972; Ling et al., Nature 321:779-782, 1986; Vale et al., Nature 321 :776-779, 1986; Mason et al., Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad. Sci. USA 83:3091-3095, 1986. 6.7.8. CHEMOTACTIC/CHEMOKINETIC ACTIVITY A protein ofthe present invention may have chemotactic or chemokinetic activity (e.g., act as a chemokine) for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells. A polynucleotide ofthe invention can encode a polypeptide exhibiting such attributes. Chemotactic and chemokinetic proteins can be used to mobilize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent. A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indirectly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known assay for cell chemotaxis. The activity of a protein ofthe invention may, among other means, be measured by the following methods: Assays for chemotactic activity (which will identify proteins that induce or prevent chemotaxis) consist of assays that measure the ability of a protein to induce the migration of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population. Suitable assays for movement and adhesion include, without limitation, those described in: Cuπent Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Marguiles, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376, 1995; Lind et al. APMIS 103:140-146, 1995; Muller et al Eur. J. Immunol. 25:1744-1748; Gruber et al. J. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of Immunol. 153:1762-1768, 1994. 6.7.9. HEMOSTATIC AND THROMBOLYTIC ACTIVITY A protein ofthe invention may also exhibit hemostatic or thrombolytic activity. A polynucleotide ofthe invention can encode a polypeptide exhibiting such attributes. Such a protein is expected to be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein ofthe invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke). The activity of a protein ofthe invention may, among other means, be measured by the following methods : Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; Burdick et al., Thrombosis Res. 45:413-419, 1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474, 1988. 6.7.10. RECEPTOR/LIGAND ACTIVITY A protein ofthe present invention may also demonstrate activity as receptors , receptor ligands or inhibitors or agonists of receptor/ligand interactions. A polynucleotide ofthe invention can encode a polypeptide exhibiting such characteristics. Examples of such receptors and ligands include, without limitation, cytokine receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including without limitation, cellular adhesion molecules (such as selectins, integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses). Receptors and ligands are also useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. A protein ofthe present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions. The activity of a protein ofthe invention may, among other means, be measured by the following methods: Suitable assays for receptor-ligand activity include without limitation those described in: Cuπent Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987; Bierer et al., J. Exp. Med. 168:1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994; Stitt et al., Cell 80:661-670, 1995. By way of example, the novel Interleukin -1 Receptor Antagonist ofthe invention may be used as a ligand for a cytokine receptor thereby modulating the biological activity of that receptor. Examples of cytokine receptors that may be used include, but are not limited to, the Interleukin-1 Type I or the Interleukin-Type II Receptor. Whether the novel Interleukin -1 Receptor Antagonist ofthe invention exhibits agonist, partial agonist, antagonist, or partial antagonist activity for a particular receptor, such as a cytokine receptor, in a particular cell type can be determined by conventional techniques known to those skilled in the art. In one embodiment, one or more cells expressing a cytokine receptor (e.g., Interleukin-1 Type I or Type π Receptors) are contacted with the protein ofthe invention. Examples of cells that may be contacted with the protein ofthe invention include, but are not limited to, mammalian cells such as fibroblasts and T-cells. Preferably the novel protein ofthe invention acts as an antagonist for a cytokine receptor (e.g.-the Interleukin-I Receptor) so that the biological activities of that receptor are inhibited. Studies characterizing drugs or proteins as agonist or antagonist or partial agonists a partial antagonist require the use of other proteins as competing ligands. The novel protein ofthe present invention exhibit an affinity for Interleukin-1 Receptor. Thus, the proteins of the present invention may be used, for example, as competitors in assays involving Interleukin-1 Receptors (e.g., Example 12). Alternatively ,the protein of the invention may be labeled by being coupled to radioisotopes, colorimetric molecules or a toxin molecules by conventional methods. ("Guide to Protein Purification" Muπay P. Deutscher (ed) Methods in Enzymology Vol. 182 (1990) Academic Press, Inc. San Diego) and used in both in vivo and in vitro to bind to the Interleukin-1 Receptor. Examples of radioisotopes include, but are not limited to, tritium and carbon- 14 . Examples of colorimetric molecules include, but are not limited to, fluorescent molecules such as fluorescamine, or rhodamine or other colorimetric molecules. Examples of toxins include, but are not limited, to riacin. By way of example, the proteins coupled to such molecules are useful in studies involving in vivo or in vitro metabolism ofthe Interleukin-1 Receptor. 6.7.11 DRUG SCREENING WITH THE NOVEL INTERLEUKIN-1 RECEPTOR ANTAGONIST POLYPEPTIDES. This invention is particularly useful for screening compounds by using the novel Interleukin-1 Receptor Antagonist polypeptides or binding fragments thereof in any of a variety of drug screening techniques. The novel Interleukin-1 receptor antagonist polypeptides or fragments employed in such a test may either be free in solution, affixed to a solid support, borne on a cell surface or located intracellularly. One method of drug screening utilizes eukaryotic or prokaryotic host cells which are stably transformed with recombinant nucleic acids expressing the polypeptide or fragment. Drugs are screened against such transformed cells in competitive binding assays. Such cells, either in viable or fixed form, can be used for standard binding assays. One may measure, for example, the formation of complexes between novel Interleukin-1 receptor antagonist polypeptides or fragments and the agent being tested or examine the diminution in complex formation between the novel Interleukin-1 receptor antagonist polypeptides and an appropriate cell line, which are well known in the art. 6.7.11.1 ASSAY FOR ANTI-INTERLEUKIN-1 RECEPTOR ACTIVITY In one embodiment, the Interleukin-1 receptor antagonist activity ofthe polypeptides ofthe invention is determined using a method that involve (1) forming a mixture comprising Interleukin-1, the Interleukin-1 receptor, and the Interleukin-1 receptor antagonist polypeptides ofthe invention and/or its agonists and antagonists (or agonist or antagonist drug candidates) and/or antibodies specific for the Interleukin-1 receptor antagonist polypeptides ofthe invention; (2) incubating the mixture under conditions whereby, but for the presence of said Interleukin-1 receptor antagonist polypeptide ofthe invention and/or its agonists and antagonists (or agonist or antagonist drug candidates) and or antibodies specific for the Interleukin-1 receptor antagonist polypeptides ofthe invention, the Interleukin-1 binds to the Interleukin-1 receptor; and (3) detecting the presence or absence of specific binding of Interleukin-1 to the Interleukin-1 receptor. 6.7.11.2 ASSAY FOR ANTAGONISTS AND AGONISTS Human HepG2 cells are incubated at 37 degree(s) C. for 18-24 hours in serum- free Dulbecco's modified Eagle medium. Separate monolayers of cells are incubated in the same medium supplemented with Interleukin-1 at various concentrations and in the same medium supplemented with Interleukin-1 receptor antagonists ofthe invention at various concentrations. Monolayers are rinsed vigorously with isotonic buffer and incubated in (35-S) methionine, 250 mu ci/ml methionine-free medium and pulsed for a period of 15-30 minutes to assess net synthesis. Cell culture fluid is discarded and monolayers are again rinsed and resuspended in cell lysis buffer. The newly synthesized radiolabeled hepatic proteins in these cell lysates are detected by immunoprecipitation, SDS-PAGE and fluorography. 6.7.12. ANTI-INFLAMMATORY ACTIVITY Proteins ofthe present invention may also exhibit anti-inflammatory activity. The anti-inflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell interactions (such as, for example, cell adhesion), by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting cell extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Proteins exhibiting such activities can be used to treat inflammatory conditions including chronic or acute conditions), including without limitation intimation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting from over production of cytokines such as TNF or IL-1. Proteins ofthe invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material. In particular, the Interleukin-1 receptor antagonist of this invention may be utilized to prevent or treat condition such as, but not limited to, utilized, for example, as part of methods for the prevention and/or treatment of disorders involving sepsis, acute pancreatitis, endotoxic shock, cytokine induced shock, rheumatoid arthritis, chronic inflammatory arthritis, pancreatic cell damage from diabetes mellitus type 1, graft versus host disease, inflammatory bowel disease, inflamation associated with pulmonary disease, including bronchitis and chronic bronchitis, other autoimmune disease or inflammatory disease, including allergies and in particular chronic allergies, an antiproliferative agent such as for acute or chronic myelogenous leukemia or in the prevention of premature labor secondary to intrauterine infections. 6.7.12.1. REGULATION OF IL-13 ANTI-INFLAMMATORY ACTIVITY ILl-Hyl proteins ofthe invention can induce expression ofthe anti- inflammatory cytokine IL-13. As a result, IL-1 Hyl polynucleotides or polypeptides, or antagonists of IL-1 Hyl activity can be used for therapeutic intervention in any of the numerous pathological states in which IL-13 activity has been implicated. For example, recent animal model data suggest that IL-13 is a central cytokine in promoting atopic asthma [Ahmed et al., Exp Clin Immunogenet 17(l):18-22 (2000)], through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity [Heinzmann et al.,Hum Mol Genet 9(4):549-59 (2000)]. Certain variants of IL-13 signaling are likely to be important promoters of human asthma [Heinzmann et al.,Hum Mol Genet 9(4):549-59 (2000)]. IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma in a manner that is independent of immunoglobulin E and eosinophils. [Wills-Kaφ et al., Science 282(5397):2258-61 (1998)]. Inhibition of IL-13 activity through administration of IL-lHyl antagonists is thus expected to reduce the adverse effects of asthma. Other data, however, indicates that IL-13 (but not human IL-4) exhibits an anti-inflammatory action in the airways of TNF-alpha- or antigen-challenged guinea pigs, by mechanisms that may involve the decreased generation of eosinophil-stimulating activity in the airways [Watson et al., J.Respir. Cell Mol Biol 20(5): 1007-12 (1999)]. IL-13 may play a role in the pathogenesis of both atopic and nonatopic asthma, at least partly through promoting recruitment of eosinophils to the bronchial mucosa [Humbert et al.,J Allergy Clin Immunol 99(5):657-65 (1997)]. Administration of IL-13 has been suggested as a potential therapeutic approach in the prevention of type 1 diabetes [Kretowski et al, Scand J Immunol 51(3):321-5 (2000)]. IL-13 treatment on development of type 1 diabetes in diabetes-prone nonobese diabetic (NOD) mice indicated that hIL-13 is capable of downregulating immunomflammatory diabetogenic pathways in NOD mice [Zaccone et al, Diabetes 48(8): 1522-8 (1999)]. Administration of IL-Hyl polynucleotides, polypeptides and agonists is therefore expected to be useful for preventing or treating type I diabetes. Recent evidence suggests a role for IL-12 and IL-13 in modulating allergic responses and support the notion that the clinical effects of glucocorticoids are at least partially mediated through the modulation of cytokine production [Naseer et al., Am J Respir Crit Care Med 155(3):845-51(1997)]. Additional evidence indicates a distinct role for IL-13 in mediating the physiologic response to a diverse aπay of allergens and parasites [Cony, Cuπ Opin immunol 11(6):610-4 (1999)]. For example, IL-13 has been shown to be a key factor in determining susceptibility to Leishmania major infection as indicated by data showing that IL-13 in transgenic mice makes the normally resistant C57BL/6 mouse strain susceptible to L. major infection even in the absence of IL-4 expression [Matthews et al., J Immunol 164(3): 1458-62 (2000)]. Similarly, the role of IL-13 in helminth- induced inflammation and protective immunity against nematode infections was demonstrated in recent observations which indicated that IL-13 can have equal or even greater importance than IL-4 in inflammatory responses and host protection against infection [Finkelman et al., Cuπ Opin Immunol 1999 Aug;l l(4):420-6 ]. Also, data suggests a role for IL-13 in resistance to intestinal nematode infection [Bancroft et al, J Immunol 160(7):3453-61 (1998)]. Still other data suggest that IL-13 expression is a prominent feature ofthe allergen-induced late nasal response (LNR), and that inhibition of the LNR following steroid therapy may be partly attributable to inhibition of IL-13 expression. [Ghaffar et al.,Am J Respir Cell Mol Biol 17(1): 17-24 (1997)]. Increased IL-13 expression is also an important feature of allergic and nonallergic patients with chronic sinusitis [al Ghamdi et al., J Otolaryngol 26(3):160-6 (1997)]. IL-13 may play some role in the development of atopic dermatitis (AD) [Takamatsu et al., Dermatology 196(4):377-81 (1998)]. Levels of mRNA for IL-13 were significantly greater in PBMC of patients with AD than in controls, suggesting that an increase in IL-13 expression may regulate the in vivo synthesis of IgE in patients with AD. [Katagiri et al., Clin Exp Immunol 108(2):289-94 (1997)]. IL-13 also provides protection from LPS-induced lethal endotoxemia in a manner that is similar to but independent from that of EL- 10, and therefore can be added to the list of cytokine immunomodulators that might be beneficial in the treatment of septic shock. [Muchamuel et al., J Immunol 158(6):2898-903 (1997)]. IL-13 (0.5 microgram/mouse) dramatically reduced the lethal effects of lipopolysaccharide (LPS) if administered either 24 or 4 h prior to or concomitantly with LPS challenge [Nicoletti et al., Eur J Immunol 27(6):1580-3 (1997)]. Administration of IL-lHyl polynucleotides, polypeptides or other agonists is thus expected to protect against the adverse effects of endotoxemia. IL-13 has also been reported to suppress various aspects ofthe pathophysiology of arthritis. [Evans et al., Intern Med 38(3):233-9 (1999)], and administration of IL- IHyl polynucleotides, polypeptides or other agonists is thus expected to be useful for treating arthritis. Involvement of IL-13 has also been implicated is numerous other pathological states. For example, data suggests a role for interleukin 13 in Hodgkin's disease [Flicker, Mol Med Today 5(11):463 (1999)]. IL-13 activates STAT6 and inhibits liver injury induced by ischemia reperfusion. IL-13 suppresses liver neutrophil recruitment, hepatocellular injury, and liver edema were each reduced [Yoshidome et al., Am J Pathol 155(4): 1059-64 (1999)]. Administration of IL-13 appears to be promising for treatment for severe uveitis [Roberge et al., Br J Ophthalmol 82(10):1195-8 (1998)]. An interleukin 13 (IL-13) receptor has also be observed to be overexpressed in several ADDS-KS cell lines examined. [Husain et la., Clin Cancer Res 3(2):151-6 (1997)]. Th2 cytokines, such as IL-13, play a part in the development of Kimura's disease [Katagiri et al., Br J Dermatol 137(6):972-7 (1997)]. Results have suggested that reduced amounts of IL-13 in the peritoneal fluid of women with endometriosis may lead to a lack of suppression of macrophage activation, thereby contributing to the overall pathogenesis of this disease [McLaren et al., Hum Reprod 12(6):1307-10 (1997)]. IL-13 may be a serologic indicator of systemic inflammation in patients with systemic sclerosis (SSc). [Hasegawa et al., J Rheumatol 24(2):328-32 (1997)]. 6.7.12.2 MODULATION OF IL-18, IL-12 and IFN-γ RELATED DISORDERS Administration of IL-lHyl polynucleotides, polypeptides and agonists is also expected to be useful for the treatment of IL-18 and or IL-12 and/or IFN-γ related disorders. IL-lHyl inhibits IL-18 and IL-12 activity, including IL-18 and IL-12 induced IFN-γ production. IL-18 has been found to have a variety of biological activities including the stimulation of activated T cell proliferation, enhancement of NK cell lytic activity, induction of IFNγ secretion, enhancement of Fas ligand expression and function, and stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production by activated T cells. IL-18 has been shown to counteract viral and intracellular infections and suppress tumor formation. However, IL-18 is also involved in the pathogenic progression of chronic inflammatory diseases, including endotoxin- induced shock, liver injury (including endotoxin-induced liver injury, hepatitis, biliary atresia and obesity-related fatty liver) and autoimmune diseases. Other disorders related to IL-18 production include meliodosis, purine nucleoside phosphorylase deficiency, increased susceptibility to Leishmania major and Staphylococcus aureus infection, hemophagocytic lymphohistiocytosis, mononucleosis, viral meningitis/encephalitis, bacterial meningitis/encephalitis and ischemia or ischemia/reperfusion injury. Inflammation may result from infection with pathogenic organisms (including gram-positive bacteria, gram-negative bacteria, viruses, fungi, and parasites such as protozoa and helminths), transplant rejection (including rejection of solid organs such as kidney, liver, heart, lung or cornea, as well as rejection of bone maπow transplants including graft versus host disease (GVHD)), or from localized chronic or acute autoimmune or allergic reactions. Autoimmune diseases include acute glomerulonephritis; rheumatoid or reactive arthritis; chronic glomerulonephritis; inflammatory bowel diseases such as Crohn's disease, ulcerative colitis and necrotizing enterocolitis; granulocyte transfusion associated syndromes; inflammatory dermatoses such as contact dermatitis, atopic dermatitis, psoriasis; systemic lupus erythematosus (SLE), autoimmune thyroiditis, multiple sclerosis, some forms of diabetes, or any other autoimmune state where attack by the subject's own immune system results in pathologic tissue destruction. Allergic reactions include allergic asthma, chronic bronchitis, allergic rhinitis, acute and delayed hypersensitivity. Systemic inflammatory disease states include inflammation associated with trauma, burns, reperfusion following ischemic events (e.g. thrombotic events in heart, brain, intestines or peripheral vasculature, including myocardial infarction and stroke), sepsis, ARDS or multiple organ dysfunction syndrome. Inflammatory cell recruitment also occurs in atherosclerotic plaques. Endotoxin activation ofthe systemic inflammatory response leads to a number of disorders including bacterial and/or endotoxin-related shock, fever, tachycardia, tachypnea, cytokine overstimulation, increased vascular permeability, hypotension, complement activation, disseminated intravascular coagulation, anemia, thrombocytopenia, leukopenia, pulmonary edema, adult respiratory distress syndrome, intestinal ischemia, renal insufficiency and failure, and metabolic acidosis. Hepatitis represents liver disorders that are characterized by hepatic inflammation and necrosis that can be manifested as an acute or chronic condition. These liver disorders include virus-induced hepatitis such as hepatitis A, hepatitis B, hepatitis C (non-A, non-B hepatitis), hepatitis D, hepatitis E; toxin and drug induced hepatitis such as acetaminophohen hepatotoxicity, halothane hepatotoxicity, mehtyldopa hepatoxicity, iaoniazid hepatoxicity, sodium valproate hepatoxicity, phenytion hepatoxicity, chloφromazine hepatoxicity, amiodarone hepatoxicity, amioidarone hepatoxicity, erythromycin hepatoxicity, oral contraceptive hepatoxicity, 17,α-alkyl-substituted anabolic steroid hepatoxicity and trimethoprim- sulfamethoxazole hepatoxicity; cholestatic hepatitis; alcoholic hepatitis; autoimmune chronic active hepatitis; and T cell mediated hepatitis. Other conditions that cause liver injury include congenital bilary atresia, obesity-related fatty liver and the autosomal recessive disease heamophagocytic lymphohistocytosis (HLH). IL-18 induced IFN-γ plays a role in liver injury. IFNγ has been shown to mediate LPS-induced liver injury following Propionibacterium acnes infection as described in Tsuji et al. (J. Immunol. 162: 1049-55, 1999). Large number of macrophages and lymphocytes infiltrate the portal area in response to P. acnes infection which results in intrahepatic formation of granulomas. IFNγ knock out mice exhibited less macrophage infiltration and a reduction in the number and size of granulomas. Subsequent treatment with low doses of LPS caused massive hepatic necrosis and increased IL-12, IL-18 and TNF-α serum levels in the normal mice, while the knock out mice exhibited drastic decreases in IL-12, IL-18 and TNF-α serum levels. The addition of IFNγ neutralizing antibody also caused a decrease in IL-18 and IL-12 levels. This model of liver injury indicates that LPS-induced liver injury is associated with increased levels of IL-18, IL-12 and IFN-γ. Cuπently, a role for IL-lβ is not known in this liver injury model. Since IL-lβ is known to be induced by LPS, it is possible IL-lβ also plays a role in the disorder. Treatment with IL-Ra may modulate the severity of liver injury due to IL-18 induced JFN-y production and IL-lβ. IL-18 has also been shown to be involved in the immunomediated hepatitis model where treatment with concavalin A induced hepatitis in mice as described by Fiorucci et al. (Gastroenterology 118: 404-21, 2000). In this model, CD+ Tcells and Thl -like cytokines cause Fas mediated liver cell death. Treatment with a nitric oxide derivative of aspirin protected against this cell death by reducing production of IFNγ, IL-18, IL-12, D_-lβ and TNF-α. In addition, a neutralizing antibody to IL-18 caused a decrease in IFNγ production and reduced liver injury induced by conA. HLH is a fatal autosomal recessive disease that manifests in early childhood. This disease is characterized by fever, hepatosplenomegaly, cytopenia and widespread infiltration of vital organs by activated lymphocytes and macrophages. Patients with HLH exhibit elevated serum levels of IL-18. IL-18 plays an important role in the induction of Thl cells in HLH patients. (Takada et al., Br. J. Haematol. 106: 182-9, 1999). JL-lHyl inhibits IL-18 induced production of IFNγ. In the models described above, the degree of IL-1 β activity is not known. Since IL-1 β is known to be induced by LPS, it is possible that D_,-l β also play a role in the pafhogenicity of these conditions. The presence of the appropriate amount of IL-lHyl polynucleotides, polypeptides or other agonists may modulate the severity ofthe disease states due to both IL-18 induced IFNγ production and IL-lβ. IL-12 is known to potentiate IFNγ production, and the cytolytic activity of NK cells and cytotoxic T lymphocytes. These immunomodulatory effects have implicated a role for IL-12 in therapies for cancer and infectious disease. However, these same therapeutic effects can also promote autoimmune diseases and chronic inflammatory conditions such as multiple sclerosis, transplant rejection and cytotoxicity. EL- 12 and IFN-γ are involved in the pathogenesis of multiple sclerosis (MS). In the experimental allergic encephalomyelitis animal model (EAE), the demyelinating effect on the central nervous system is carried out similar to that in humans suffering from MS. Cuπently, IFNβ is used to treat MS. The mechanism of IFNβ treatment may be to decrease the number of EFNγ producing T cells in MS patients. (Rep et al., J. Neuroimmunol. 96:92-100, 1999). In addition, IFNγ production in blood lymphocytes was found to coπelate with disability score in MS patients. (Petcreit et al., Mult. Scler. 6: 19-23, 2000). Antibodies against IL-12 were found to prevent superantigen-induced and spontaneous relapses of EAE in mice (Constantineseu et al., J. Immunol. 161 : 5097-5104, 1998). All these studies point to the involvement of IL-12 induced EFNγ production in the progression of MS in human patients. Therefore, treatment with IL-lHyl polynucleotides, polypeptides or other agonists to reduce IFNγ production may be an useful therapy for MS patients. The combination of IL-12 and IL-2 has synergistic anti -tumor activity in vivo. However, in clinical trials the combination resulted in significant toxicity and subsequently shock and mortality. (Cohen, Science 270: 908 1995). In a murine model investigated by Carson et al. (J. Immunol., 162: 4943-5, 1999) determined that the fatal systemic inflammatory response was NK cell dependent but not related to other effector molecules in the system such as IL-1, TNF-α, and IFNγ. EL- IHyl polynucleotides, polypeptides or other agonists is expected to inhibit EL- 12 induced EFN-γ production and is expected to inhibit other biological activities of IL-12 such as NK cell cytolytic activity. Inhibition of NK cell activity, through IL-Ra administration, may reduce toxicity resulting from IL- 12 antitumor treatment. The effect of IL-lHyl on EL- 12 and or EL- 18 activity may be determined by measuring the biological activities of these cytokines. Both IL-12 and IL-18 are known to induce IFNγ production in T cells. In addition to IFN-γ, the combination of IL-12 and EL-18 increases production of IL-3, IL-6 and TNF. Treatment with IL-lHyl is expected to reduce IFNγ production induced by IL-12 and EL-18. Circulating or local levels of IFNγ in tissue or fluid samples from patients treated with IL-lHyl polynucleotides, polypeptides or other agonists will be an indication ofthe therapeutic effects of EL- IHyl on the IL-18 and IL-12 related disorders. Tissue samples include tissue samples from an area involved in inflammation or other disease. Fluid samples include, for example, whole blood, plasma, serum, cerebrospinal fluid, synovial fluid, peritoneal fluids (including lavage fluids or exudate), pleural fluids (including lavage fluids or exudate), wound fluids (including lavage fluids or exudate). Furthermore, IL-12 is known to activate NK cells and to decrease serum IgE levels. These assays may also be used to measure the effectiveness of EL-lHyl treatment for IL-12 related disorders. The NK cell cytolytic activity in patients treated with IL-lHyl polynucleotides, polypeptides or other agonists can be assayed by measuring patient's blood samples ability to lysis colon carcinoma or lymphoma cells in vitro. (Lieberman et al., J. Sur. Res., 50: 410-415, 1992) In addition, the serum levels of IgE from patients treated with EL- IHyl can be measured to determine the effectiveness of treatment for EL-12 related disorders. (Kiniwa et al. J. Clin. Invest., 90 : 262-66, 1992) 6.7.13. LEUKEMIAS Leukemias and related disorders may be treated or prevented by administration of a therapeutic that promotes or inhibits function ofthe polynucleotides and/or polypeptides ofthe invention. Such leukemias and related disorders include but are not limited to acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, myeloblastic, promyelocytic, myelomonocytic, monocytic, erythroleukemia, chronic leukemia, chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia (for a review of such disorders, see Fishman et al., 1985, Medicine, 2d Ed., J.B. Lippincott Co., Philadelphia). 6.7.14. NERVOUS SYSTEM DISORDERS Nervous system disorders, involving cell types which can be tested for efficacy of intervention with compounds that modulate the activity ofthe polynucleotides and/or polypeptides ofthe invention, and which can be treated upon thus observing an indication of therapeutic utility, include but are not limited to nervous system injuries, and diseases or disorders which result in either a disconnection of axons, a diminution or degeneration of neurons, or demyelination. Nervous system lesions which may be treated in a patient (including human and non-human mammalian patients) according to the invention include but are not limited to the following lesions of either the central (including spinal cord, brain) or peripheral nervous systems: (i) traumatic lesions, including lesions caused by physical injury or associated with surgery, for example, lesions which sever a portion ofthe nervous system, or compression injuries; (ii) ischemic lesions, in which a lack of oxygen in a portion ofthe nervous system results in neuronal injury or death, including cerebral infarction or ischemia, or spinal cord infarction or ischemia; (iii) infectious lesions, in which a portion ofthe nervous system is destroyed or injured as a result of infection, for example, by an abscess or associated with infection by human immunodeficiency virus, heφes zoster, or heφes simplex virus or with Lyme disease, tuberculosis, syphilis; (iv) degenerative lesions, in which a portion ofthe nervous system is destroyed or injured as a result of a degenerative process including but not limited to degeneration associated with Parkinson's disease, Alzheimer's disease, Huntington's chorea, or amyotrophic lateral sclerosis; (v) lesions associated with nutritional diseases or disorders, in which a portion ofthe nervous system is destroyed or injured by a nutritional disorder or disorder of metabolism including but not limited to, vitamin B12 deficiency, folic acid deficiency, Wernicke disease, tobacco-alcohol amblyopia, Marchiafava-Bignami disease (primary degeneration ofthe coφus callosum), and alcoholic cerebellar degeneration; (vi) neurological lesions associated with systemic diseases including but not limited to diabetes (diabetic neuropathy, Bell's palsy), systemic lupus erythematosus, carcinoma, or sarcoidosis; (vii) lesions caused by toxic substances including alcohol, lead, or particular neurotoxins; and (viii) demyelinated lesions in which a portion ofthe nervous system is destroyed or injured by a demyelinating disease including but not limited to multiple sclerosis, human immunodeficiency virus-associated myelopathy, transverse myelopathy or various etiologies, progressive multifocal leukoencephalopathy, and central pontine myelinolysis. Therapeutics which are useful according to the invention for treatment of a nervous system disorder may be selected by testing for biological activity in promoting the survival or differentiation of neurons. For example, and not by way of limitation, therapeutics which elicit any ofthe following effects may be useful according to the invention: (i) increased survival time of neurons in culture; (ii) increased sprouting of neurons in culture or in vivo; (iii) increased production of a neuron-associated molecule in culture or in vivo, e.g., choline acetyltransferase or acetylcholinesterase with respect to motor neurons; or (iv) decreased symptoms of neuron dysfunction in vivo. Such effects may be measured by any method known in the art. In prefeπed, non-limiting embodiments, increased survival of neurons may be measured by the method set forth in Arakawa et al. (1990, J. Neurosci. 10:3507-3515); increased sprouting of neurons may be detected by methods set forth in Pestronk et al. (1980, Exp. Neurol. 70:65-82) or Brown et al. (1981, Ann. Rev. Neurosci. 4:17-42); increased production of neuron-associated molecules may be measured by bioassay, enzymatic assay, antibody binding, Northern blot assay, etc., depending on the molecule to be measured; and motor neuron dysfunction may be measured by assessing the physical manifestation of motor neuron disorder, e.g., weakness, motor neuron conduction velocity, or functional disability. In a specific embodiments, motor neuron disorders that may be treated according to the invention include but are not limited to disorders such as infarction, infection, exposure to toxin, trauma, surgical damage, degenerative disease or malignancy that may affect motor neurons as well as other components ofthe nervous system, as well as disorders that selectively affect neurons such as amyotrophic lateral sclerosis, and including but not limited to progressive spinal muscular atrophy, progressive bulbar palsy, primary lateral sclerosis, infantile and juvenile muscular atrophy, progressive bulbar paralysis of childhood (Fazio-Londe syndrome), poliomyelitis and the post polio syndrome, and Hereditary Motorsensory Neuropathy (Charcot-Marie-Tooth Disease). 6.7.15. OTHER ACTIVITIES A protein ofthe invention may also exhibit one or more ofthe following additional activities or effects: inhibiting the growth, infection or function of, or killing, infectious agents, including, without limitation, bacteria, viruses, fungi and other parasites; effecting (suppressing or enhancing) bodily characteristics, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape); effecting biorhythms or caricadic cycles or rhythms; effecting the fertility of male or female subjects; effecting the metabolism, catabolism, anabolism, processing, utilization, storage or elimination of dietary fat, lipid, protein, carbohydrate, vitamins, minerals, co-factors or other nutritional factors or component(s); effecting behavioral characteristics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors; providing analgesic effects or other pain reducing effects; promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, coπecting deficiencies ofthe enzyme and treating deficiency-related diseases; treatment of hypeφroliferative disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein. 6.8. THERAPEUTIC METHODS The novel Interleukin-1 Receptor Antagonist ofthe invention has numerous applications in a variety of therapeutic methods. Examples of therapeutic applications include, but are not limited to, those exemplified below. 6.8.1 SEPSIS One embodiment ofthe invention is the administration of an effective amount ofthe Interleukin-1 receptor antagonist polypeptides of the invention to individuals that are at a high risk of developing sepsis, or that have developed sepsis. An example ofthe former category are patients about to undergo surgery. While the mode of administration is not particularly important, parenteral administration is prefeπed because ofthe rapid progression of sepsis, and thus, the need to have the inhibitor disseminate quickly throughout the body. Thus, the prefeπed mode of administration is to deliver an LV. bolus slightly before, during, or after surgery. The dosage ofthe Interleukin-1 receptor antagonist polypeptides of the invention will normally be determined by the prescribing physician. It is to be expected that the dosage will vary according to the age, weight and response ofthe individual patient. Typically, the amount of inhibitor administered per dose will be in the range of about 0.1 to 25 mg/kg of body weight, with the prefeπed dose being about 0.1 to 10 mg/kg of patient body weight. For parenteral administration, the Interleukin-1 receptor antagonist polypeptides ofthe invention will be formulated in an injectable form combined with a pharmaceutically acceptable parenteral vehicle. Such vehicles are well known in the art and examples include water, saline, Ringer's solution, dextrose solution, and solutions consisting of small amounts ofthe human serum albumin. The vehicle may contain minor amounts of additives that maintain the isotonicity and stability ofthe inhibitor. The preparation of such solutions is within the skill ofthe art. Typically, the cytokine inhibitor will be formulated in such vehicles at a concentration of about 1-8 mg/ml to about 10 mg/ml. 6.8.2 ARTHRITIS AND INFLAMMATION The immunosuppressive effects ofthe Interleukin-1 inhibitor against rheumatoid arthritis is determined in an experimental animal model system. The experimental model system is adjuvant induced arthritis in rats, and the protocol is described by J. Holoshitz, et at., 1983, Science, 219:56, or by B. Waksman et al., 1963, Int. Arch. Allergy Appl. Immunol., 23:129. Induction ofthe disease can be caused by a single injection, generally intradermally, of a suspension of killed Mycobacterium tuberculosis in complete Freund's adjuvant (CFA). The route of injection can vary, but rats may be injected at the base ofthe tail with an adjuvant mixture. The inhibitor is administered in phosphate buffered solution (PBS) at a dose of about 1-5 mg/kg. The control consists of administering PBS only. The procedure for testing the effects ofthe Interleukin-1 inhibitor would consist of intradermally injecting killed Mycobacterium tuberculosis in CFA followed by immediately administering the inhibitor and subsequent treatment every other day until day 24. At 14, 15, 18, 20, 22, and 24 days after injection of Mycobacterium CFA, an overall arthritis score may be obtained as described by J. Holoskitz above. An analysis ofthe data would reveal that the inhibitor would have a dramatic affect on the swelling of the joints as measured by a decrease ofthe arthritis score. 6.8.3 DIABETES Interleukin-1 has been shown to be involved in the destruction of islet cells in diabetes mellitus (DM) (Mandrup-Paulsen, T., K. Bendtzen, J. Nerup, C. A. Dinarello, M. Svenson, and J. H. Nielson [1986] Diabetologia 29:63-67). The Interleukin-1 receptor antagonist polypeptides ofthe invention limit lymphocyte and macrophage mediated damage to islet cells in incipient cases of DM identified by disease susceptibility via genetic background and family history. The inflammatory destruction ofthe pancreatic beta islet cells in such individuals with early DM is reduced by parenterally administering the Interleukin-1 receptor antagonist polypeptides ofthe invention which have an anti-Interleukin-1 effect in the pancreas. 6.8.4 ANTI-HYPOTENSIVE ARGININE-FREE FORMULATIONS The parenteral formulation ofthe therapeutic regimen is defined as including: about 3-4 g/l isoleucine, about 4-6 g/l leucine, about 3-4 g/l lysine, about 1-2 g/l methionine, about 1-2 g/l phenylalanine, about 2-3 g l threonine, about 0.5-1.5 g/l tryptophan, about 3-4 g/l valine, about 4-5 g/l alanine, about 1-2 g/l histidine, about 3-4 g/l proline, about 1-2 g/l serine, about 0.25-0.75 g/l tyrosine, about 4-5 g/l glycine and about 2-3 g/l aspartic acid, together in a pharmacologically acceptable excipient. In another prefeπed embodiment ofthe described parenteral formulation, the formulation may further include ornithine, most particularly at a concentration of about 1-2 g/l . In still another embodiment ofthe described parenteral formulation, the formulation may include citrulline, most preferably at a concentration of between about 1 g/l and about 2 g/l. Both citrulline and ornithine may be included in still another embodiment ofthe formulation, again at the concentrations indicated. The method includes an arginine-free formulation which comprises the amino acids and concentrations thereof already described herein, together in a pharmacologically acceptable excipient. Again, the formulation may further include ornithine, citrulline, or both, to even further supply physiologically required concentrations of urea cycle substrates in the animal. Most preferably, the formulation is provided as a parenteral formulation. Another aspect ofthe method comprises a method for treating chemotherapeutic agent-related hypotension. In a most prefeπed embodiment, the method comprises monitoring an animal receiving a chemotherapeutic agent for a decrease in systolic blood pressure to less than about 100 mm Hg to detect an animal with systemic hypotension, treating the animal having systemic hypotension with a therapeutic regimen comprising a therapeutically effective amount of an arginine-free formulation sufficient to reduce plasma or serum arginine concentrations administered concuπently with or followed by the administration of a therapeutically effective concentration of an interleukin-1 receptor antagonist, and maintaining the animal on the therapeutic regimen until an increase of systolic blood pressure to at least about 100 mm Hg is detectable. Most preferably, the arginine-free formulation is a parenteral formulation. In a prefeπed embodiment, the interleukin-1 receptor antagonist polypeptide of the invention is used in combination with the anti-hypotensive arginine free formulation to treat hypotension in an animal, particularly that hypotension caused by exposure to endotoxin or septic shock. A patient having a systolic blood pressure of less than about 100 mm Hg will be targeted for the present treatment. Such a patient is to be placed on a continuous feed of an arginine-free formulation which includes a mixture of essential and nonessential amino acids as described in U.S. Patent NO. 5,334,380. The patient is treated concuπently with the interleukin-1 Hyl receptor antagonist polypeptides ofthe invention. Blood samples are to be obtained from the patient and arginine levels in the serum or plasma fraction are determined. 6.9 PHARMACEUTICAL FORMULATIONS AND ROUTES OF ADMINISTRATION A protein ofthe present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources) may be administered to a patient in need, by itself, or in pharmaceutical compositions where it is mixed with suitable carriers or excipient(s) at doses to treat or ameliorate a variety of disorders. Such a composition may also contain (in addition to protein and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term "pharmaceutically acceptable" means a non-toxic material that does not interfere with the effectiveness ofthe biological activity ofthe active ingredient(s). The characteristics ofthe carrier will depend on the route of administration. The pharmaceutical composition ofthe invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, D.-9, D_-10, IL-11, IL-12, IL-13, IL-14, IL-15, IFN, G-CSF, Meg-CSF, thrombopoietm, stem cell factor, and erythropoietin. The pharmaceutical composition may further contain other agents which either enhance the activity ofthe protein or complement its activity or use in treatment. Such additional factors and/or agents may be included in the pharmaceutical composition to produce a synergistic effect with protein ofthe invention, or to minimize side effects. Proteins that can be administered with IL-lHyl include other IL-1 receptor antagonist polypeptides such as IL-lra and IL-lHy2, described in U.S. Serial No. 09/316,081 filed May 20, 1999. Conversely, protein ofthe present invention may be included in formulations ofthe particular cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent to minimize side effects ofthe cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent. A protein ofthe present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins. As a result, pharmaceutical compositions ofthe invention may comprise a protein ofthe invention in such multimeric or complexed form. Techniques for formulation and administration ofthe compounds ofthe instant application may be found in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, latest edition. A therapeutically effective dose further refers to that amount ofthe compound sufficient to result in amelioration of symptoms, e.g., treatment, healing, prevention or amelioration ofthe relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient, administered alone, a therapeutically effective dose refers to that ingredient alone. When applied to a combination, a therapeutically effective dose refers to combined amounts ofthe active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously. In practicing the method of treatment or use ofthe present invention, a therapeutically effective amount of protein ofthe present invention is administered to a mammal having a condition to be treated. Protein ofthe present invention may be administered in accordance with the method ofthe invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, protein ofthe present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein ofthe present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors. 6.9.1. ROUTES OF ADMINISTRATION Suitable routes of administration may, for example, include oral, rectal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections. Administration of protein ofthe present invention used in the pharmaceutical composition or to practice the method ofthe present invention can be carried out in a variety of conventional ways, such as oral ingestion, inhalation, topical application or cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection. Intravenous administration to the patient is prefeπed. Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection ofthe compound directly into a arthritic joints or in fibrotic tissue, often in a depot or sustained release formulation. In order to prevent the scarring process frequently occurring as complication of glaucoma surgery, the compounds may be administered topically, for example, as eye drops. Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with a specific antibody, targeting, for example, arthritic or fibrotic tissue. The liposomes will be targeted to and taken up selectively by the afflicted tissue. 6.9.2. COMPOSITIONS/FORMULATIONS Pharmaceutical compositions for use in accordance with the present invention thus may be formulated in a conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. These pharmaceutical compositions may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. Proper formulation is dependent upon the route of administration chosen. When a therapeutically effective amount of protein ofthe present invention is administered orally, protein ofthe present invention will be in the form of a tablet, capsule, powder, solution or elixir. When administered in tablet form, the pharmaceutical composition of the invention may additionally contain a solid carrier such as a gelatin or an adjuvant. The tablet, capsule, and powder contain from about 5 to 95% protein ofthe present invention, and preferably from about 25 to 90% protein of the present invention. When administered in liquid form, a liquid carrier such as water, petroleum, oils of animal or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic oils may be added. The liquid form ofthe pharmaceutical composition may further contain physiological saline solution, dextrose or other saccharide solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90% by weight of protein ofthe present invention, and preferably from about 1 to 50% protein ofthe present invention. When a therapeutically effective amount of protein ofthe present invention is administered by intravenous, cutaneous or subcutaneous injection, protein ofthe present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution. The preparation of such parenterally acceptable protein solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A prefeπed pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein ofthe present invention, an isotonic vehicle such as Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer's Injection, or other vehicle as known in the art. The pharmaceutical composition ofthe present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art. For injection, the agents ofthe invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. For transmucosal administration, penetrants appropriate to the baπier to be permeated are used in the formulation. Such penetrants are generally known in the art. For oral administration, the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such caπiers enable the compounds ofthe invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated. Pharmaceutical preparations for oral use can be obtained solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyπolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyπolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Dragee cores are provided with suitable coatings. For this puφose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyπolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses. Pharmaceutical preparations which can be used orally include push- fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for such administration. For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner. For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix ofthe compound and a suitable powder base such as lactose or starch. The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Pharmaceutical formulations for parenteral administration include aqueous solutions ofthe active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity ofthe suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility ofthe compounds to allow for the preparation of highly concentrated solutions. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides. In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. A pharmaceutical carrier for the hydrophobic compounds ofthe invention is a cosolvent system comprising benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. The cosolvent system may be the VPD co-solvent system. VPD is a solution of 3% w/v benzyl alcohol, 8% w/v ofthe nonpolar surfactant polysorbate 80, and 65% w/v polyethylene glycol 300, made up to volume in absolute ethanol. The VPD co-solvent system (VPD:5W) consists of VPD diluted 1 :1 with a 5% dextrose in water solution. This co-solvent system dissolves hydrophobic compounds well, and itself produces low toxicity upon systemic administration. Naturally, the proportions of a co-solvent system may be varied considerably without destroying its solubility and toxicity characteristics. Furthermore, the identity ofthe co-solvent components may be varied: for example, other low-toxicity nonpolar surfactants may be used instead of polysorbate 80; the fraction size of polyethylene glycol may be varied; other biocompatible polymers may replace polyethylene glycol, e.g. polyvinyl pyπolidone; and other sugars or polysaccharides may substitute for dextrose. Alternatively, other delivery systems for hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well known examples of delivery vehicles or carriers for hydrophobic drugs. Certain organic solvents such as dimethylsulfoxide also may be employed, although usually at the cost of greater toxicity. Additionally, the compounds may be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various of sustained-release materials have been established and are well known by those skilled in the art. Sustained-release capsules may, depending on their chemical nature, release the compounds for a few weeks up to over 100 days. Depending on the chemical nature and the biological stability ofthe therapeutic reagent, additional strategies for protein stabilization may be employed. The pharmaceutical compositions also may comprise suitable solid or gel phase carriers or excipients. Examples of such caπiers or excipients include but are not limited to calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols. Many ofthe compounds ofthe invention may be provided as salts with pharmaceutically compatible counterions. Such pharmaceutically acceptable base addition salts are those salts which retain the biological effectiveness and properties ofthe free acids and which are obtained by reaction with inorganic or organic bases such as sodium hydroxide, magnesium hydroxide, ammonia, trialkylamine, dialkylamine, monoalkylamine, dibasic amino acids, sodium acetate, potassium benzoate, triethanol amine and the like. The pharmaceutical composition ofthe invention may be in the form of a complex ofthe protein(s) of present invention along with protein or peptide antigens. The protein and/or peptide antigen will deliver a stimulatory signal to both B and T lymphocytes. B lymphocytes will respond to antigen through their surface immunoglobulin receptor. T lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation ofthe antigen by MHC proteins. MHC and structurally related proteins including those encoded by class I and class D MHC genes on host cells will serve to present the peptide antigen(s) to T lymphocytes. The antigen components could also be supplied as purified MHC-peptide complexes alone or with co-stimulatory molecules that can directly signal T cells. Alternatively antibodies able to bind surface immunoglobulin and other molecules on B cells as well as antibodies able to bind the TCR and other molecules on T cells can be combined with the pharmaceutical composition ofthe invention. The pharmaceutical composition ofthe invention may be in the form of a liposome in which protein ofthe present invention is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Preparation of such liposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Pat. NOs. 4,235,871 ; 4,501,728; 4,837,028; and 4,737,323, all of which are incoφorated herein by reference. The amount of protein ofthe present invention in the pharmaceutical composition ofthe present invention will depend upon the nature and severity ofthe condition being treated, and on the nature of prior treatments which the patient has undergone. Ultimately, the attending physician will decide the amount of protein ofthe present invention with which to treat each individual patient. Initially, the attending physician will administer low doses of protein ofthe present invention and observe the patient's response. Larger doses of protein ofthe present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not increased further. It is contemplated that the various pharmaceutical compositions used to practice the method ofthe present invention should contain about 0.01 μg to about 100 mg (preferably about 0.1 μg to about 10 mg, more preferably about 0.1 μg to about 1 mg) of protein ofthe present invention per kg body weight. For compositions ofthe present invention which are useful for bone, cartilage, tendon or ligament regeneration, the therapeutic method includes administering the composition topically, systematically, or locally as an implant or device. When administered, the therapeutic composition for use in this invention is, of course, in a pyrogen-free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage. Topical administration may be suitable for wound healing and tissue repair. Therapeutically useful agents other than a protein ofthe invention which may also optionally be included in the composition as described above, may alternatively or additionally, be administered simultaneously or sequentially with the composition in the methods ofthe invention. Preferably for bone and/or cartilage formation, the composition would include a matrix capable of delivering the protein-containing composition to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body. Such matrices may be formed of materials presently in use for other implanted medical applications. The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties. The particular application ofthe compositions will define the appropriate formulation. Potential matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tricalciumphosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyanhydrides. Other potential materials are biodegradable and biologically well-defined, such as bone or dermal collagen. Further matrices are comprised of pure proteins or extracellular matrix components. Other potential matrices are nonbiodegradable and chemically defined, such as sintered hydroxyapatite, bioglass, aluminates, or other ceramics. Matrices may be comprised of combinations of any of the above mentioned types of material, such as polylactic acid and hydroxyapatite or collagen and tricalciumphosphate. The bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability. Presently prefeπed is a 50:50 (mole weight) copolymer of lactic acid and glycolic acid in the form of porous particles having diameters ranging from 150 to 800 microns. In some applications, it will be useful to utilize a sequestering agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matrix. A prefeπed family of sequestering agents is cellulosic materials such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl-methylcellulose, and carboxymethylcellulose, the most prefeπed being cationic salts of carboxymethylcellulose (CMC). Other prefeπed sequestering agents include hyaluronic acid, sodium alginate, poly(ethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and poly(vinyl alcohol). The amount of sequestering agent useful herein is 0.5-20 wt %, preferably 1-10 wt % based on total formulation weight, which represents the amount necessary to prevent desorbtion ofthe protein from the polymer matrix and to provide appropriate handling ofthe composition, yet not so much that the progenitor cells are prevented from infiltrating the matrix, thereby providing the protein the opportunity to assist the osteogenic activity ofthe progenitor cells. In further compositions, proteins ofthe invention may be combined with other agents beneficial to the treatment ofthe bone and/or cartilage defect, wound, or tissue in question. These agents include various growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF-. alpha, and TGF-.beta.), and insulin-like growth factor (IGF). The therapeutic compositions are also presently valuable for veterinary applications. Particularly domestic animals and thoroughbred horses, in addition to humans, are desired patients for such treatment with proteins ofthe present invention. The dosage regimen of a protein-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considering various factors which modify the action ofthe proteins, e.g., amount of tissue weight desired to be formed, the site of damage, the condition ofthe damaged tissue, the size of a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical factors. The dosage may vary with the type of matrix used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition. For example, the addition of other known growth factors, such as IGF I (insulin like growth factor 1), to the final composition, may also effect the dosage. Progress can be monitored by periodic assessment of tissue/bone growth and or repair, for example, X-rays, histomoφhometric determinations and tetracycline labeling. Polynucleotides ofthe present invention can also be used for gene therapy. Such polynucleotides can be introduced either in vivo or ex vivo into cells for expression in a mammalian subject. Polynucleotides ofthe invention may also be administered by other known methods for introduction of nucleic acid into a cell or organism (including, without limitation, in the form of viral vectors or naked DNA). Cells may also be cultured ex vivo in the presence of proteins ofthe present invention in order to proliferate or to produce a desired effect on or activity in such cells. Treated cells can then be introduced in vivo for therapeutic puφoses. 6.9.3. EFFECTIVE DOSAGE Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients are contained in an effective amount to achieve its intended puφose. More specifically, a therapeutically effective amount means an amount effective to prevent development of or to alleviate the existing symptoms ofthe subject being treated. Determination ofthe effective amounts is well within the capability of those skilled in the art, especially in light ofthe detailed disclosure provided herein. For any compound used in the method ofthe invention, the therapeutically effective dose can be estimated initially from cell culture assays. For example, a dose can be formulated in animal models to achieve a circulating concentration range that includes the IC 50 as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. A therapeutically effective dose refers to that amount ofthe compound that results in amelioration of symptoms or a prolongation of survival in a patient. Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD 50 (the dose lethal to 50% ofthe population) and the ED 50 (the dose therapeutically effective in 50% ofthe population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio between LD 50 and ED 50 . Compounds which exhibit high therapeutic indices are prefeπed. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED 50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view ofthe patient's condition. See, e.g., Fingl et al., 1975, in "The Pharmacological Basis of Therapeutics", Ch. 1 p.l . Dosage amount and interval may be adjusted individually to provide plasma levels ofthe active moiety which are sufficient to maintain the desired therapeutic effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vitro data; for example, the concentration necessary to achieve 50-90% inhibition of cytokine activity using the assays described herein. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations. Dosage intervals can also be determined using MEC value. Compounds should be administered using a regimen which maintains plasma levels above the MEC for 10-90% ofthe time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration. The amount of composition administered will, of course, be dependent on the subject being treated, on the subject's weight, the severity ofthe affliction, the manner of administration and the judgment ofthe prescribing physician. 6.9.4. PACKAGING The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Compositions comprising a compound ofthe invention formulated in a compatible pharmaceutical caπier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. 6.10. ANTIBODIES Another aspect ofthe mvention is an antibody that specifically binds the polypeptide ofthe invention. Such antibodies can be either monoclonal or polyclonal antibodies, as well fragments thereof and humanized forms or fully human forms, such as those produced in transgenic animals. The invention further provides a hybridoma that produces an antibody according to the invention. Antibodies ofthe invention are useful for detection and/or purification ofthe polypeptides ofthe invention. Protein ofthe invention may also be used to immunize animals to obtain polyclonal and monoclonal antibodies which specifically react with the protein. Such antibodies may be obtained using either the entire protein or fragments thereof as an immunogen. The peptide immunogens additionally may contain a cysteine residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, as in R. P. Merrifield, J. Amer. Chem. Soc. 85, 2149-2154 (1963); J. L. Krstenansky, et al., FEBS Lett. 211, 10 (1987). Monoclonal antibodies binding to the protein ofthe invention may be useful diagnostic agents for the immunodetection of the protein. Neutralizing monoclonal antibodies binding to the protein may also be useful therapeutics for both conditions associated with the protein and also in the treatment of some forms of cancer where abnormal expression ofthe protein is involved. In the case of cancerous cells or leukemic cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread ofthe cancerous cells, which may be mediated by the protein. In general, techniques for preparing polyclonal and monoclonal antibodies as well as hybridomas capable of producing the desired antibody are well known in the art (Campbell, A.M., Monoclonal Antibodies Technology: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984); St. Groth et al., J. Immunol. 35:1-21 (1990); Kohler and Milstein, Nature 256:495-497 (1975)), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., Immunology Today 4:72 (1983); Cole et al., in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985), pp. 77-96). Any animal (mouse, rabbit, etc.) which is known to produce antibodies can be immunized with a peptide or polypeptide ofthe invention. Methods for immunization are well known in the art. Such methods include subcutaneous or intraperitoneal injection ofthe polypeptide. One skilled in the art will recognize that the amount of the protein encoded by the ORF ofthe present invention used for immunization will vary based on the animal which is immunized, the antigenicity ofthe peptide and the site of injection. The protein that is used as an immunogen may be modified or administered in an adjuvant in order to increase the protein's antigenicity. Methods of increasing the antigenicity of a protein are well known in the art and include, but are not limited to, coupling the antigen with a heterologous protein (such as globulin or β-galactosidase) or through the inclusion of an adjuvant during immunization. For monoclonal antibodies, spleen cells from the immunized animals are removed, fused with myeloma cells, such as SP2/0-Agl4 myeloma cells, and allowed to become monoclonal antibody producing hybridoma cells. Any one of a number of methods well known in the art can be used to identify the hybridoma cell which produces an antibody with the desired characteristics. These include screening the hybridomas with an ELISA assay, western blot analysis, or radioimmunoassay (Lutz et al., Exp. Cell Research. 175:109-124 (1988)). Hybridomas secreting the desired antibodies are cloned and the class and subclass is determined using procedures known in the art (Campbell, A.M., Monoclonal Antibody Technology: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984)). Techniques described for the production of single chain antibodies (U.S. Patent 4,946,778) can be adapted to produce single chain antibodies to proteins ofthe present invention. For polyclonal antibodies, antibody containing antiserum is isolated from the immunized animal and is screened for the presence of antibodies with the desired specificity using one ofthe above-described procedures. The present invention further provides the above-described antibodies in delectably labeled form. Antibodies can be delectably labeled through the use of radioisotopes, affinity labels (such as biotin, avidin, etc.), enzymatic labels (such as horseradish peroxidase, alkaline phosphatase, etc.) fluorescent labels (such as FITC or rhodamine, etc.), paramagnetic atoms, etc. Procedures for accomplishing such labeling are well-known in the art, for example, see (Sternberger, L.A. et al., J. Histochem. Cytochem. 18:315 (1970); Bayer, E.A. et al., Meth. Enzym. 62:308 (1979); Engval, E. et al., Immunol. 109:129 (1972); Goding, J.W. J. Immunol. Meth. 13:215 (1976)). The labeled antibodies ofthe present invention can be used for in vitro, in vivo, and in situ assays to identify cells or tissues in which a fragment ofthe polypeptide of interest is expressed. The antibodies may also be used directly in therapies or other diagnostics. The present invention further provides the above-described antibodies immobilized on a solid support. Examples of such solid supports include plastics such as polycarbonate, complex carbohydrates such as agarose and sepharose, acrylic resins and such as polyacrylamide and latex beads. Techniques for coupling antibodies to such solid supports are well known in the art (Weir, D.M. et al., "Handbook of Experimental Immunology'' 4th Ed., Blackwell Scientific Publications, Oxford, England, Chapter 10 (1986); Jacoby, W.D. et al., Meth. Enzym. 34 Academic Press, N.Y. (1974)). The immobilized antibodies ofthe present invention can be used for in vitro, in vivo, and in situ assays as well as for immuno-affinity purification ofthe proteins ofthe present invention. 6.11. COMPUTER READABLE SEQUENCES In one application of this embodiment, a nucleotide sequence ofthe present invention can be recorded on computer readable media. As used herein, "computer readable media" refers to any medium which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A skilled artisan can readily appreciate how any ofthe presently known computer readable mediums can be used to create a manufacture comprising computer readable medium having recorded thereon a nucleotide sequence ofthe present invention. As used herein, "recorded" refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any ofthe presently known methods for recording information on computer readable medium to generate manufactures comprising the nucleotide sequence information ofthe present invention. A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide sequence ofthe present invention. The choice ofthe data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information ofthe present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and Microsoft Word, or represented in the form of an ASCD file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of dataprocessor structuring formats (e.g. text file or database) in order to obtain computer readable medium having recorded thereon the nucleotide sequence information ofthe present invention. By providing the nucleotide sequence of SEQ TD NOS: 1, 2, 4, 6 or 7 or a representative fragment thereof, or a nucleotide sequence at least 99.9% identical to SEQ DD NOS: 1, 2 , 4, 5, 6 or 7 or 8 in computer readable form, a skilled artisan can routinely access the sequence information for a variety of puφoses. Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium. The examples which follow demonstrate how software which implements the BLAST (Altschul et al., J. Mol. Biol. 215:403-410 (1990)) and BLAZE (Brutlag et al., Comp. Chem. 17:203-207 (1993)) search algorithms on a Sybase system is used to identify open reading frames (ORFs) within a nucleic acid sequence. Such ORFs may be protein encoding fragments and may be useful in producing commercially important proteins such as enzymes used in fermentation reactions and in the production of commercially useful metabolites. As used herein, "a computer-based system" refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information ofthe present invention. The minimum hardware means ofthe computer-based systems ofthe present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one ofthe cuπently available computer-based systems are suitable for use in the present invention. As stated above, the computer-based systems ofthe present invention comprise a data storage means having stored therein a nucleotide sequence ofthe present invention and the necessary hardware means and software means for supporting and implementing a search means. As used herein, "data storage means" refers to memory which can store nucleotide sequence information ofthe present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information ofthe present invention. As used herein, "search means" refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means. Search means are used to identify fragments or regions of a known sequence which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based systems ofthe present invention. Examples of such software includes, but is not limited to, MacPattern (EMBL), BLASTN and BLASTA (NPOLYPEPTEDEIA). A skilled artisan can readily recognize that any one ofthe available algorithms or implementing software packages for conducting homology searches can be adapted for use in the present computer-based systems. As used herein, a "target sequence" can be any nucleic acid or amino acid sequence of six or more nucleotides or two or more amino acids. A skilled artisan can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occuπence in the database. The most prefeπed sequence length of a target sequence is from about 10 to 100 amino acids or from about 30 to 300 nucleotide residues. However, it is well recognized that searches for commercially important fragments, such as sequence fragments involved in gene expression and protein processing, may be of shorter length. As used herein, "a target structural motif," or "target motif," refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration which is formed upon the folding ofthe target motif. There are a variety of target motifs known in the art. Protein target motifs include, but are not limited to, enzyme active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, promoter sequences, haiφin structures and inducible expression elements (protein binding sequences). 6.12. TRIPLE HELIX FORMATION In addition, the fragments ofthe present invention, as broadly described, can be used to control gene expression through triple helix formation or antisense DNA or RNA, both of which methods are based on the binding of a polynucleotide sequence to DNA or RNA. Polynucleotides suitable for use in these methods are usually 20 to 40 bases in length and are designed to be complementary to a region ofthe gene involved in transcription (triple helix - see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 15241:456 (1988); and Dervan et al., Science 251 :1360 (1991)) or to the mRNA itself (antisense - Olmno, J. Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL (1988)). Triple helix- formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences ofthe present invention is necessary for the design of an antisense or triple helix oligonucleotide. 6.13. DIAGNOSTIC ASSAYS AND KITS The present invention further provides methods to identify the presence or expression of one ofthe ORFs ofthe present invention, or homolog thereof, in a test sample, using a nucleic acid probe or antibodies ofthe present invention. In general, methods for detecting a polynucleotide of the invention can comprise contacting a sample with a compound that binds to and forms a complex with the polynucleotide for a period sufficient to form the complex, and detecting the complex, so that if a complex is detected, a polynucleotide ofthe invention is detected in the sample. Such methods can also comprise contacting a sample under stringent hybridization conditions with nucleic acid primers that anneal to a polynucleotide of the invention under such conditions, and amplifying annealed polynucleotides, so that if a polynucleotide is amplified, a polynucleotide ofthe invention is detected in the sample. In general, methods for detecting a polypeptide ofthe invention can comprise contacting a sample with a compound that binds to and forms a complex with the polypeptide for a period sufficient to form the complex, and detecting the complex, so that if a complex is detected, a polypeptide of the invention is detected in the sample. In detail, such methods comprise incubating a test sample with one or more ofthe antibodies or one or more of nucleic acid probes ofthe present invention and assaying for binding ofthe nucleic acid probes or antibodies to components within the test sample. Conditions for incubating a nucleic acid probe or antibody with a test sample vary. Incubation conditions depend on the format employed in the assay, the detection methods employed, and the type and nature ofthe nucleic acid probe or antibody used in the assay. One skilled in the art will recognize that any one ofthe commonly available hybridization, amplification or immunological assay formats can readily be adapted to employ the nucleic acid probes or antibodies ofthe present invention. Examples of such assays can be found in Chard, T., An Introduction to Radioimmunoassay and Related Techniques, Elsevier Science Publishers, Amsterdam, The Netherlands (1986); Bullock, G.R. et al., Techniques in Emmunocytochemistry, Academic Press, Orlando, FL Vol. 1 (1982), Vol. 2 (1983), Vol. 3 (1985); Tijssen, P., Practice and Theory of immunoassays: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1985). The test samples ofthe present invention include cells, protein or membrane extracts of cells, or biological fluids such as sputum, blood, serum, plasma, or urine. The test sample used in the above-described method will vary based on the assay format, nature ofthe detection method and the tissues, cells or extracts used as the sample to be assayed. Methods for preparing protein extracts or membrane extracts of cells are well known in the art and can be readily be adapted in order to obtain a sample which is compatible with the system utilized. In another embodiment ofthe present invention, kits are provided which contain the necessary reagents to carry out the assays ofthe present invention. Specifically, the invention provides a compartment kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one ofthe probes or antibodies ofthe present invention; and (b) one or more other containers comprising one or more ofthe following: wash reagents, reagents capable of detecting presence of a bound probe or antibody. In detail, a compartment kit includes any kit in which reagents are contained in separate containers. Such containers include small glass containers, plastic containers or strips of plastic or paper. Such containers allows one to efficiently transfer reagents from one compartment to another compartment such that the samples and reagents are not cross-contaminated, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another. Such containers will include a container which will accept the test sample, a container which contains the antibodies used in the assay, containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and containers which contain the reagents used to detect the bound antibody or probe. Types of detection reagents include labeled nucleic acid probes, labeled secondary antibodies, or in the alternative, if the primary antibody is labeled, the enzymatic, or antibody binding reagents which are capable of reacting with the labeled antibody. One skilled in the art will readily recognize that the disclosed probes and antibodies ofthe present invention can be readily incoφorated into one of the established kit formats which are well known in the art. 6.14. SCREENING ASSAYS Using the isolated proteins and polynucleotides ofthe invention, the present invention further provides methods of obtaining and identifying agents which bind to a polypeptide encoded by the ORF from a polynucleotide with a sequence of SEQ TD NOS: 1, 2, 4, 6, 7 or 8 to a specific domain ofthe polypeptide encoded by the nucleic acid, or to a nucleic acid with a sequence of SEQ ED NOS: 1, 2 4, 6, 7 or 8. In detail, said method comprises the steps of: (a) contacting an agent with an isolated protein encoded by an ORF of the present invention, or nucleic acid ofthe invention; and (b) determining whether the agent binds to said protein or said nucleic acid. In general, therefore, such methods for identifying compounds that bind to a polynucleotide ofthe invention can comprise contacting a compound with a polynucleotide of the invention for a time sufficient to form a polynucleotide/compound complex, and detecting the complex, so that if a polynucleotide/compound complex is detected, a compound that binds to a polynucleotide ofthe invention is identified. Likewise, in general, therefore, such methods for identifying compounds that bind to a polypeptide ofthe invention can comprise contacting a compound with a polypeptide ofthe invention for a time sufficient to form a polypeptide/compound complex, and detecting the complex, so that if a polypeptide/compound complex is detected, a compound that binds to a polynucleotide ofthe invention is identified. Methods for identifying compounds that bind to a polypeptide ofthe invention can also comprise contacting a compound with a polypeptide ofthe invention in a cell for a time sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a receptor gene sequence in the cell, and detecting the complex by detecting reporter gene sequence expression, so that if a polypeptide/compound complex is detected, a compound that binds a polypeptide ofthe invention is identified. Compounds identified via such methods can include compounds which modulate the activity of a polypeptide ofthe invention (that is, increase or decrease its activity, relative to activity observed in the absence ofthe compound). Alternatively, compounds identified via such methods can include compounds which modulate the expression of a polynucleotide ofthe invention (that is, increase or decrease expression relative to expression levels observed in the absence ofthe compound). Compounds, such as compounds identified via the methods of the invention, can be tested using standard assays well known to those of skill in the art for their ability to modulate activity/expression. The agents screened in the above assay can be, but are not limited to, peptides, carbohydrates, vitamin derivatives, or other pharmaceutical agents. The agents can be selected and screened at random or rationally selected or designed using protein modeling techniques. For random screening, agents such as peptides, carbohydrates, pharmaceutical agents and the like are selected at random and are assayed for their ability to bind to the protein encoded by the ORF ofthe present invention. Alternatively, agents may be rationally selected or designed. As used herein, an agent is said to be "rationally selected or designed" when the agent is chosen based on the configuration ofthe particular protein. For example, one skilled in the art can readily adapt cuπently available procedures to generate peptides, pharmaceutical agents and the like capable of binding to a specific peptide sequence in order to generate rationally designed antipeptide peptides, for example see Hurby et al., Application of Synthetic Peptides: Antisense Peptides," In Synthetic Peptides, A User's Guide, W.H. Freeman, NY (1992), pp. 289-307, and Kaspczak et al., Biochemistry 28:9230-8 (1989), or pharmaceutical agents, or the like. In addition to the foregoing, one class of agents of the present invention, as broadly described, can be used to control gene expression through binding to one ofthe ORFs or EMFs ofthe present invention. As described above, such agents can be randomly screened or rationally designed/selected. Targeting the ORF or EMF allows a skilled artisan to design sequence specific or element specific agents, modulating the expression of either a single ORF or multiple ORFs which rely on the same EMF for expression control. One class of DNA binding agents are agents which contain base residues which hybridize or form a triple helix formation by binding to DNA or RNA. Such agents can be based on the classic phosphodiester, ribonucleic acid backbone, or can be a variety of sulfhydryl or polymeric derivatives which have base attachment capacity. Agents suitable for use in these methods usually contain 20 to 40 bases and are designed to be complementary to a region ofthe gene involved in transcription (triple helix - see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251 :1360 (1991)) or to the mRNA itself (antisense - Okano, J. Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL (1988)). Triple helix- formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences ofthe present invention is necessary for the design of an antisense or triple helix oligonucleotide and other DNA binding agents. Agents which bind to a protein encoded by one ofthe ORFs ofthe present invention can be used as a diagnostic agent, in the control of bacterial infection by modulating the activity ofthe protein encoded by the ORF. Agents which bind to a protein encoded by one ofthe ORFs ofthe present invention can be formulated using known techniques to generate a pharmaceutical composition. 6.15. USE OF NUCLEIC ACIDS AS PROBES Another aspect ofthe subject invention is to provide for polypeptide-specific nucleic acid hybridization probes capable of hybridizing with naturally occurring nucleotide sequences. The hybridization probes ofthe subject invention may be derived from the nucleotide sequence ofthe SEQ ID NOS: 1, 2, 4, 6, 7 or 8. Because the coπesponding gene is only expressed in a limited number of tissues, especially adult tissues, a hybridization probe derived from SEQ ED NOS: 1, 2, 4, 6, 7, or 8 can be used as an indicator ofthe presence of RNA of cell type of such a tissue in a sample. Any suitable hybridization technique can be employed, such as, for example, in situ hybridization. PCR as described US Patent NOs 4,683,195 and 4,965,188 provides additional uses for oligonucleotides based upon the nucleotide sequences. Such probes used in PCR may be of recombinant origin, may be chemically synthesized, or a mixture of both. The probe will comprise a discrete nucleotide sequence for the detection of identical sequences or a degenerate pool of possible sequences for identification of closely related genomic sequences. Other means for producing specific hybridization probes for nucleic acids include the cloning of nucleic acid sequences into vectors for the production of mRNA probes. Such vectors are known in the art and are commercially available and may be used to synthesize RNA probes in vitro by means ofthe addition ofthe appropriate RNA polymerase as T7 or SP6 RNA polymerase and the appropriate radioactively labeled nucleotides. The nucleotide sequences may be used to construct hybridization probes for mapping their respective genomic sequences. The nucleotide sequence provided herein may be mapped to a chromosome or specific regions of a chromosome using well known genetic and/or chromosomal mapping techniques. These techniques include in situ hybridization, linkage analysis against known chromosomal markers, hybridization screening with libraries or flow-sorted chromosomal preparations specific to known chromosomes, and the like. The technique of fluorescent in situ hybridization of chromosome spreads has been described, among other places, in Verma et al (1988) Human Chromosomes: A Manual of Basic Techniques, Pergamon Press, New York NY. Fluorescent in situ hybridization of chromosomal preparations and other physical chromosome mapping techniques may be coπelated with additional genetic map data. Examples of genetic map data can be found in the 1994 Genome Issue of Science (265 : 1981 f). Coπelation between the location of a nucleic acid on a physical chromosomal map and a specific disease (or predisposition to a specific disease) may help delimit the region of DNA associated with that genetic disease. The nucleotide sequences ofthe subject invention may be used to detect differences in gene sequences between normal, carrier or affected individuals. The nucleotide sequence may be used to produce purified polypeptides using well known methods of recombinant DNA technology. Among the many publications that teach methods for the expression of genes after they have been isolated is Goeddel (1990) Gene Expression Technology, Methods and Enzymology, Vol 185, Academic Press, San Diego. Polypeptides may be expressed in a variety of host cells, either prokaryotic or eukaryotic. Host cells may be from the same species from which a particular polypeptide nucleotide sequence was isolated or from a different species. Advantages of producing polypeptides by recombinant DNA technology include obtaining adequate amounts of the protein for purification and the availability of simplified purification procedures. 14.1 Preparation of Sequencing Chips and Arrays A basic example is using 6-mers attached to 50 micron surfaces to give a chip with dimensions of 3 x 3 mm which can be combined to give an aπay of 20 x 20 cm. Another example is using 9-mer oligonucleotides attached to 10 x 10 microns surface to create a 9-mer chip, with dimensions of 5 x 5 mm. 4000 units of such chips may be used to create a 30 x 30 cm aπay. In an aπay in which 4,000 to 16,000 oligochips are arranged into a square array. A plate, or collection of tubes, as also depicted, may be packaged with the aπay as part ofthe sequencing kit. The aπays may be separated physically from each other or by hydrophobic surfaces. One possible way to utilize the hydrophobic strip separation is to use technology such as the Iso-Grid Microbiology System produced by QA Laboratories, Toronto, Canada. Hydrophobic grid membrane filters (HGMF) have been in use in analytical food microbiology for about a decade where they exhibit unique attractions of extended numerical range and automated counting of colonies. One commercially-available grid is ISO-GRDD™ from QA Laboratories Ltd. (Toronto, Canada) which consists of a square (60 x 60 cm) of polysulfone polymer (Gelman Tuffryn HT-450, 0.45u pore size) on which is printed a black hydrophobic ink grid consisting of 1600 (40 x 40) square cells. HGMF have previously been inoculated with bacterial suspensions by vacuum filtration and incubated on the differential or selective media of choice. Because the microbial growth is confined to grid cells of known position and size on the membrane, the HGMF functions more like an MPN apparatus than a conventional plate or membrane filter. Peterkin et al. (1987) reported that these HGMFs can be used to propagate and store genomic libraries when used with a HGMF replicator. One such instrument replicates growth from each ofthe 1600 cells ofthe ISO-GRDD and enables many copies ofthe master HGMF to be made (Peterkin et al, 1987). Shaφe et al. (1989) also used ISO-GRDD HGMF form QA Laboratories and an automated HGMF counter (MI- 100 Enteφreter) and RP-100 Replicator. They reported a technique for maintaining and screening many microbial cultures. Peterkin and colleagues later described a method for screening DNA probes using the hydrophobic grid-membrane filter (Peterkin et al, 1989). These authors reported methods for effective colony hybridization directly on HGMFs. Previously, poor results had been obtained due to the low DNA binding capacity ofthe epoxysulfone polymer on which the HGMFs are printed. However, Peterkin et al (1989) reported that the binding of DNA to the surface ofthe membrane was improved by treating the replicated and incubated HGMF with polyethyleneimine, a polycation, prior to contact with DNA. Although this early work uses cellular DNA attachment, and has a different objective to the present invention, the methodology described may be readily adapted for Format 3 SBH. In order to identify useful sequences rapidly, Peterkin et al. (1989) used radiolabeled plasmid DNA from various clones and tested its specificity against the,. DNA on the prepared HGMFs. In this way, DNA from recombinant plasmids was rapidly screened by colony hybridization against 100 organisms on HGMF replicates which can be easily and reproducibly prepared. Manipulation with small (2-3 mm) chips, and parallel execution of thousands ofthe reactions. The solution ofthe invention is to keep the chips and the probes in the corresponding aπays. In one example, chips containing 250,000 9-mers are synthesized on a silicon wafer in the form of 8 x 8 mM plates (15 uM/oligonucleotide, Pease et al., 1994) arrayed in 8 x 12 format (96 chips) with a 1 mM groove in between. Probes are added either by multichannel pipette or pin aπay, one probe on one chip. To score all 4000 6-mers, 42 chip aπays have to be used, either using different ones, or by reusing one set of chip aπays several times. In the above case, using the earlier nomenclature ofthe application, F=9; P=6; and F + P = 15. Chips may have probes of formula BxNn, where x is a number of specified bases B; and n is a number of non-specified bases, so that x = 4 to 10 and n = 1 to 4. To achieve more efficient hybridization, and to avoid potential influence of any support oligonucleotides, the specified bases can be suπounded by unspecified bases, thus represented by a formula such as (N)nBx(N)m. 14.2 Preparation of Support Bound Oligonucleotides Oligonucleotides, i.e., small nucleic acid segments, may be readily prepared by, for example, directly synthesizing the oligonucleotide by chemical means, as is commonly practiced using an automated oligonucleotide synthesizer. Support bound oligonucleotides may be prepared by any ofthe methods known to those of skill in the art using any suitable support such as glass, polystyrene or Teflon. One strategy is to precisely spot oligonucleotides synthesized by standard synthesizers, immobilization can be achieved using passive adsoφtion (Inouye & Hondo, 1990); using UV light (Nagata et al, 1985; Dahlen et al, 1987; Moπiey & Collins, 1989) or by covalent binding of base modified DNA (Keller et al, 1988; 1989); all references being specifically incoφorated herein. Another strategy that may be employed is the use ofthe strong biotin-streptavidin interaction as a linker. For example, Broude et al. (1994) describe the use of Biotinylated probes, although these are duplex probes, that are immobilized on streptavidin-coated magnetic beads. Streptavidin-coated beads may be purchased from Dynal, Oslo. Of course, this same linking chemistry is applicable to coating any surface with streptavidin. Biotinylated probes may be purchased from various sources, such as, e.g., Operon Technologies (Alameda, CA). Nunc Laboratories (Naperville, IL) is also selling suitable material that could be used. Nunc Laboratories have developed a method by which DNA can be covalently bound to the microwell surface termed Covalink NH. CovaLink NH is a polystyrene surface grafted with secondary amino groups (>NH) that serve as bridge-heads for further covalent coupling. CovaLink Modules may be purchased from Nunc Laboratories. DNA molecules may be bound to CovaLink exclusively at the 5'-end by a phosphoramidate bond, allowing immobilization of more than 1 pmol of DNA (Rasmussen et al, 1991). use of CovaLink NH strips for covalent binding of DNA molecules at the 5'-end has been described (Rasmussen et al., 1991). In this technology, a phosphoramidate bond is employed (Chu et al., 1983). This is beneficial as immobilization using only a single covalent bond is prefeπed. The phosphoramidate bond joins the DNA to the CovaLink NH secondary amino groups that are positioned at the end of spacer arms covalently grafted onto the polystyrene surface through a 2 nm long spacer arm. To link an oligonucleotide to CovaLink NH via an phosphoramidate bond, the oligonucleotide terminus must have a 5'-end phosphate group. It is, perhaps, even possible for biotin to be covalently bound to CovaLink and then streptavidin used to bind the probes. More specifically, the linkage method includes dissolving DNA in water (7.5 ng/ul) and denaturing for 10 min. at 95°C and cooling on ice for 10 min. Ice-cold 0.1 M 1-methylimidazole, pH 7.0 (1-Melm 7 ), is then added to a final concentration of 10 mM 1-Melm 7 . A ss DNA solution is then dispensed into CovaLink NH strips (75 ul/well) standing on ice. Carbodiimide 0.2 M l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), dissolved in 10 mM 1-Melm 7 , is made fresh and 25 ul added per well. The strips are incubated for 5 hours at 50°C. After incubation the strips are washed using, e.g., Nunc-Immuno Wash; first the wells are washed 3 times, then they are soaked with washing solution for 5 min., and finally they are washed 3 times (where in the washing solution is 0.4 N NaOH, 0.25% SDS heated to 50°C). It is contemplated that a further suitable method for use with the present invention is that described in PCT Patent Application WO 90/03382 (Southern & Maskos), incoφorated herein by reference. This method of preparing an oligonucleotide bound to a support involves attaching a nucleoside 3'-reagent through the phosphate group by a covalent phosphodiester link to aliphatic hydroxyl groups carried by the support. The oligonucleotide is then synthesized on the supported nucleoside and protecting groups removed from the synthetic oligonucleotide chain under standard conditions that do not cleave the oligonucleotide from the support. Suitable reagents include nucleoside phosphoramidite and nucleoside hydrogen phosphorate. An on-chip strategy for the preparation of DNA probe for the preparation of DNA probe aπays may be employed. For example, addressable laser-activated photodeprotection may be employed in the chemical synthesis of oligonucleotides directly on a glass surface, as described by Fodor et al. (1991), incoφorated herein by reference. Probes may also be immobilized on nylon supports as described by Van Ness et al. (1991); or linked to Teflon using the method of Duncan & Cavalier (1988); all references being specifically incoφorated herein. To link an oligonucleotide to a nylon support, as described by Van Ness et al. (1991), requires activation ofthe nylon surface via alkylation and selective activation ofthe 5'-amine of oligonucleotides with cyanuric chloride. One particular way to prepare support bound oligonucleotides is to utilize the light-generated synthesis described by Pease et al, (1994, incoφorated herein by reference). These authors used cuπent photolithographic techniques to generate aπays of immobilized oligonucleotide probes (DNA chips). These methods, in which light is used to direct the synthesis of oligonucleotide probes in high-density, miniaturized aπays, utilize photolabile 5'-protected N-acyl-deoxynucleoside phosphoramidites, surface linker chemistry and versatile combinatorial synthesis strategies. A matrix of 256 spatially defmed oligonucleotide probes may be generated in this manner and then used in the advantageous Format 3 sequencing, as described herein. 14.3 Preparation of Nucleic Acid Fragments The nucleic acids to be sequenced may be obtained from any appropriate source, such as cDNAs, genomic DNA, chromosomal DNA, microdissected chromosome bands, cosmid or YAC inserts, and RNA, including mRNA without any amplification steps. For example, Sambrook et al. (1989) describes three protocols for the isolation of high molecular weight DNA from mammalian cells (p. 9.14-9.23). DNA fragments may be prepared as clones in Ml 3, plasmid or lambda vectors and/or prepared directly from genomic DNA or cDNA by PCR or other amplification methods. Samples may be prepared or dispensed in multiwell plates. About 100-1000 ng of DNA samples may be prepared in 2-500 ml of final volume. The nucleic acids would then be fragmented by any ofthe methods known to those of skill in the art including, for example, using restriction enzymes as described at 9.24-9.28 of Sambrook et al. (1989), shearing by ultrasound and NaOH treatment. Low pressure shearing is also appropriate, as described by Schriefer et al. (1990, incoφorated herein by reference). In this method, DNA samples are passed through a small French pressure cell at a variety of low to intermediate pressures. A lever device allows controlled application of low to intermediate pressures to the cell. The results of these studies indicate that low-pressure shearing is a useful alternative to sonic and enzymatic DNA fragmentation methods. One particularly suitable way for fragmenting DNA is contemplated to be that using the two base recognition endonuclease, Cvi JI, described by Fitzgerald et al. (1992). These authors described an approach for the rapid fragmentation and fractionation of DNA into particular sizes that they contemplated to be suitable for shotgun cloning and sequencing. The present inventor envisions that this will also be particularly useful for generating random, but relatively small, fragments of DNA for use in the present sequencing technology. The restriction endonuclease CviJl normally cleaves the recognition sequence PuGCPy between the G and C to leave blunt ends. Atypical reaction conditions, which alter the specificity of this enzyme (CviJI**), yield a quasi-random distribution of DNA fragments form the small molecule pUC19 (2688 base pairs). Fitzgerald et al. (1992) quantitatively evaluated the randomness of this fragmentation strategy, using a CviJI** digest of pUC19 that was size fractionated by a rapid gel filtration method and directly ligated, without end repair, to a lac Z minus Ml 3 cloning vector. Sequence analysis of 76 clones showed that CviJI** restricts pyGCPy and PuGCPu, in addition to PuGCPy sites, and that new sequence data is accumulated at a rate consistent with random fragmentation. As reported in the literature, advantages of this approach compared to sonication and agarose gel fractionation include: smaller amounts of DNA are required (0.2-0.5 ug instead of 2-5 ug); and fewer steps are involved (no preligation, end repair, chemical extraction, or agarose gel electrophoresis and elution are needed). These advantages are also proposed to be of use when preparing DNA for sequencing by Format 3. irrespective ofthe manner in which the nucleic acid fragments are obtained or prepared, it is important to denature the DNA to give single stranded pieces available for hybridization. This is achieved by incubating the DNA solution for 2-5 minutes at 80-90°C. The solution is then cooled quickly to 2°C to prevent renaturation ofthe DNA fragments before they are contacted with the chip. Phosphate groups must also be removed from genomic DNA by methods known in the art. 14.4 Preparation of DNA Arrays Arrays may be prepared by spotting DNA samples on a support such as a nylon membrane. Spotting may be performed by using aπays of metal pins (the positions of which conespond to an aπay of wells in a microtiter plate) to repeated by transfer of about 20 nl of a DNA solution to a nylon membrane. By offset printing, a density of dots higher than the density ofthe wells is achieved. One to 25 dots may be accommodated in 1 mm 2 , depending on the type of label used. By avoiding spotting in some preselected number of rows and columns, separate subsets (subaπays) may be formed. Samples in one subaπay may be the same genomic segment of DNA (or the same gene) from different individuals, or may be different, overlapped genomic clones. Each ofthe subaπays may represent replica spotting ofthe same samples. In one example, a selected gene segment may be amplified from 64 patients. For each patient, the amplified gene segment may be in one 96-well plate (all 96 wells containing the same sample). A plate for each ofthe 64 patients is prepared. By using a 96-pin device, all samples may be spotted on one 8 x 12 cm membrane. Subaπays may contain 64 samples, one from each patient. Where the 96 subaπays are identical, the dot span may be 1 mm 2 and there may be a 1 mm space between subaπays. Another approach is to use membranes or plates (available from NUNC, Naperville, Illinois) which may be partitioned by physical spacers e.g. a plastic grid molded over the membrane, the grid being similar to the sort of membrane applied to the bottom of multiwell plates, or hydrophobic strips. A fixed physical spacer is not prefeπed for imaging by exposure to flat phosphor- storage screens or x-ray films. 14.5 Sequence comparisons Each sequence so obtained was compared to sequences in GenBank using a search algorithm developed by Applied Biosystems and incoφorated into the INHERIT™ 670 Sequence Analysis System. In this algorithm, Pattern Specification Language (developed by TRW Inc., Los Angeles, CA) was used to determine regions of homology. The three parameters that determine how the sequence comparisons run were window size, window offset, and eπor tolerance. Using a combination of these three parameters, the DNA database was searched for sequences containing regions of homology to the query sequence, and the appropriate sequences were scored with an initial value. Subsequently, these homologous regions were examined using dot matrix homology plots to distinguish regions of homology from chance matches. Smith- Waterman alignments were used to display the results ofthe homology search. Peptide and protein sequence homologies were ascertained using the INHERIT™ 670 Sequence Analysis System in a way similar to that used in DNA sequence homologies. Pattern Specification Language and parameter windows were used to search protein databases for sequences containing regions of homology that were scored with an initial value. Dot-matrix homology plots were examined to distinguish regions of significant homology from chance matches. Alternatively, BLAST, which stands for Basic Local Alignment Search Tool, is used to search for local sequence alignments (Altschul SF (1993) J Mol Evol 36:290-300; Altschul, SF et al (1990) J Mol Biol 215:403-10). BLAST produces alignments of both nucleotide and amino acid sequences to determine sequence similarity. Because ofthe local nature ofthe alignments, BLAST is especially useful in determining exact matches or in identifying homologs. Whereas it is ideal for matches which do not contain gaps, it is inappropriate for performing motif-style searching. The fundamental unit of BLAST algorithm output is the High-scoring Segment Pair (HSP). An HSP consists of two sequence fragments of arbitrary but equal lengths whose alignment is locally maximal and for which the alignment score meets or exceeds a threshold or cutoff score set by the user. The BLAST approach is to look for HSPs between a query sequence and a database sequence, to evaluate the statistical significance of any matches found, and to report only those matches which satisfy the user-selected threshold of significance. The parameter E establishes the statistically significant threshold for reporting database sequence matches. E is inteφreted as the upper bound ofthe expected frequency of chance occuπence of an HSP (or set of HSPs) within the context ofthe entire database search. Any database sequence whose match satisfies E is reported in the program output. The present invention is illustrated in the following examples. Example 1 addresses the identification of a novel interleukin-1 receptor antagonist. Example 2 addresses expression of studies of SEQ ED NO: 2 in human tissues using semi- quantitative PCR. Example 3 addresses chromosomal localization using SEQ ID NO: 2. Example 4 addresses the determination of intron/exon structure of locus coπesponding to SEQ ED NO: 2. Example 5 addresses the identification of Interleukin-1 receptor binding domain and receptor binding assays. Example 6 and 7 address the determination ofthe nucleotide sequence of IL-1 Hyl . Example 8 and 11 address the isolation and mapping ofthe EL-1 Hyl genomic clone. Example 9 addresses IL-1 Hyl expression in E. coli. Example 10 addresses the biological uses of IL-1 Hyl. Example 12 addresses recombinant protein expression and purification of EL-1 Hyl polypeptide. Example 13 addresses binding of interleukin-1 Hyl receptor antagonist to the IL-1 receptor. Example 14 addresses the confirmation of IL-1 Hyl EL-1 antagonist activity. Example 15 addresses the inhibition of IL-lβ induced 1L-6 production. Example 16 addresses the determination of IL-1 Hyl molecular mass. Example 17 addresses IL-1 Hyl expression in activated THP-1 cells. Example 18 addresses the detection of EL-1 Hyl protein expression in human tissues by immunohistochemistry. Example 19 addresses detection of EL-1 Hyl by in situ hybridization with a DNA probe. Example 20 addresses detection of EL-1 Hyl by in situ hybridization with a riboprobe. Example 21 describes induction of EL- 13 production by IL-1 Hyl. Example 22 relates to inhibition of EL-18 activity by IL-1 Hyl as measured by induction of interferon-gamma expression. Example 23 described IL-1 Hyl expression in skin fibroblast cells. Example 24 addresses IL-1 Hyl -induced ICAM-1 expression. Example 25 describes determination of a mouse genomic II- 1 Hyl sequence. Example 26 relates to animal studies involving IL-1 Hyl. Upon consideration ofthe present disclosure, one of skill in the art will appreciate that many other embodiments and variations may be made in the scope of the present invention. Accordingly, it is intended that the broader aspects ofthe present invention not be limited to the disclosure ofthe following examples. 7.0. EXAMPLES 7.1 EXAMPLE 1 A Novel Interleukin-1 Receptor Antagonist Obtained from a cDNA Library of Fetal Liver-Spleen A plurality of novel nucleic acids were obtained from the b 2 HFLS20W cDNA library prepared from human fetal liver-spleen tissue, as described in Bonaldo et al., Genome Res. 6:791-806 (1996), using standard PCR, SBH sequence signature analysis and Sanger sequencing techniques. The inserts ofthe library were amplified with PCR using primers specific for vector sequences which flank the inserts. These samples were spotted onto nylon membranes and inteπogated with oligonucleotide probes to give sequence signatures. The clones were clustered into groups of similar or identical sequences, and single representative clones were selected from each group for gel sequencing. The 5' sequence ofthe amplified inserts was then deduced using the reverse Ml 3 sequencing primer in a typical Sanger sequencing protocol. PCR products were purified and subjected to flourescent dye terminator cycle sequencing. Single pass gel sequencing was done using a 377 Applied Biosystems (ABI) sequencer. Two (2) of these inserts have been identified as novel sequences not previously obtained from this library, and not previously reported in public databases. These sequences are shown in Figure 2 as SEQ ED NO: 1 and 2. The polypeptide sequences coπesponding to these nucleic acid sequences are shown in Figure 3 as SEQ ED NO: 3. These amino acid sequences have striking homology to Interleukin-1 receptor antagonist. 7.2 EXAMPLE 2 Expression Study Using SEQ ID NO: 2 To study the role of SEQ TD NO: 2 in the regulation ofthe inflammatory response, gene expression was analyzed using a semi-quantitative polymerase chain reaction-based technique. cDNA libraries were used as sources of expressed genes from tissues of interest (three leukocyte preparations [two stimulated and one unstimulated], heart, lung, spleen, placenta, testes, fetal liver, adult liver, bone maπow, lymph node, macrophages, endothelial cells, fetal skin, and umbilical cord). Gene specific primers were used to amplify portions ofthe SEQ ED NO: 2 sequence (coπesponding to bases 105-772 and 161-690, as numbered from the 5' end of SEQ ID NO: 2) from the samples. Amplified products were separated on an agarose gel, transfeπed and chemically linked to a nylon filter. The filter was then hybridized with a radioactively labeled ( 33 Palρha-dCTP) double-stranded probe generated from the full-length SEQ TD NO: 2 sequence using a Klenow polymerase, random prime method. The filters were washed (high stringency) and used to expose a phosphorimaging screen for several hours. Bands indicated the presence of cDNA including SEQ DD NO: 2 sequences in a specific library, and thus mRNA expression in the coπesponding cell type or tissue. SEQ ED NO: 2 was expressed in a very limited set of human tissues. Ofthe 16 human tissues tested, fetal skin and umbilical cord were the only samples that provided a signal, indicating that expression of SEQ ED NO: 2 is tightly regulated. Expression of both IL-1 Ra are tightly restricted to a subset of tissues and cell types; both constitutively expressed in skin but not present in other tissues or cell types without stimulation Thus, the expression pattern of SEQ TD NO: 2 parallels that ofthe EL-1 Ra genes, indicating that the novel cytokine encoded by SEQ DD NO: 2 plays a role in the regulation ofthe inflammatory response. 7.3 EXAMPLE 3 Chromosomal Localization Study Using SEQ ID NO: 2 Chromosome mapping technologies allow investigators to link genes to specific regions of chromosomes. Chromosomal mapping was performed with the Stanford G3 Radiation Hybrid Panel (Research Genetics). The panel was screened with gene-specific primers (5' primer: CCCCACTGGATGGTGCTACTG; (SEQ TD NO: 15), 3' primer: GGGAAGAGATAGGAAAGGTAG) (SEQ ED NO: 16)that generated a sequence tag site (STS), and the results ofthe PCR screening were submitted to the Stanford Radiation Hybrid mapping email server at the Stanford Human Genome Center (SHGC). The gene position on the radiation hybrid framework map was provided by linking the STS coπesponding to SEQ ED NO: 2 with the SHGC marker with best linkage. The results indicated that SEQ ID NO: 2 is located on the long arm of chromosome 2. The STS was linked to the marker SHGC-7020 with a LOD (log of the odds) score of 12.25 and cR-1000 of 5, indicating that the STS was within 120 kb (kilobases) of this marker. SHGC-7020 is in turn located within 120 kb ofthe IL-1 Ra gene. Thus, the STS coπesponding to SEQ ED NO: 2 is located within about 240 kilobases ofthe EL-1 Ra gene and could be in close proximity to the EL-1 Ra gene. Gene family members are often linked to specific regions of chromosomes owing to intrachromosomal gene duplication events that give rise to multimember gene families during the process of evolution. The interleukin-1 gene family has been mapped to chromosome 2. More specifically, all ofthe interleukin 1 genes (EL- la, EL- lb) and the receptors (IL-1 Rl and TL-l RD), as well as the receptor antagonist EL-1 Ra, have been found to be situated on the long arm of chromosome 2. The identification of SEQ ED NO: 2 sequences in this same region establishes the physical linkage of SEQ ED NO: 2 to the interleukin-1 locus which evidences that the cytokine encoded by SEQ ED NO: 2 functions as a modulator ofthe inflammatory response. 7.4 EXAMPLE 4 Intron/Exon Structure of the Locus Corresponding to SEQ ID NO: 2 Members within gene families often maintain genomic organization by virtue ofthe fact that they arose from a common ancestral precursor. The intron/exon structure of IL-1 a, IL-lb and EL-1 Ra have been highly conserved, demonstrating that they probably arose from a common precursor gene. We have isolated a bacterial artificial chromosome (BAC) containing SEQ ED NO: 2. Using gene-specific primers we have sequenced in the 5' direction ofthe clone, delineating coding sequence (identical to SEQ TD NO: 2) and intronic sequence. The intron/exon structure is identical between IL-1 Ra and the BAC fragment containing SEQ ED NO: 2, providing evidence that these two sequences are members ofthe same family and were generated from a common gene precursor. 7.5 EXAMPLE 5 Interleukin-1 Receptor Binding Domain and Interleukin-1 Receptor Assay The receptor binding region of both EL-1 β and EL-1 Ra have been mapped an 18 amino acid region in the carboxy terminal half of the proteins (i.e., residues 88-105 of EL-lβ) by site-directed mutagenesis and protein modification studies. An amino acid alignment of SEQ TD NO: 3 with both IL-lβ and IL-1 Ra demonstrates that SEQ DD NO: 3 contains a receptor binding region. SEQ DD NO: 3 is 39% identical to IL-lRa and 22% identical (39% conserved) with D -lβ in this region. In comparison, IL-1 Ra, which is known to bind to the IL-1 receptor, is 28% identical and 50% conserved with IL-lβ in this region. The remarkable similarity between this region of SEQ DD NO: 3 and the receptor binding regions of both ILlβ and IL-lRa indicates that SEQ DD NO: 3 also contains an TL-l receptor binding region. The alignment of all three proteins in the receptor binding region is shown in Fig. 4. Because SEQ ID NO: 3 contains a D.,-1 receptor binding region, SEQ DD NO: 3 and truncated forms of SEQ DD NO: 3 that include the receptor binding region are useful as reagents to identify cells and tissues expressing IL-1 receptors. The IL-1 receptor binding assay described in Hannum et al. Nature 343:336-340 (1990) is used. Briefly, highly radioactive recombinant SEQ ID NO: 3 is prepared by growing E. coli expressing SEQ ID NO: 3 on M9 medium containing [35S] sulphate and purifying the labeled SEQ DD NO: 3 by chromatography on a Mono-S column. The labeled SEQ DD NO: 3 is incubated with the cells or tissue under standard IL-1 binding assay conditions, and [35S] binding. Significant [35S] binding indicates the presence of IL-1 receptors. 7.6 EXAMPLE 6 Determination of a Nucleotide Sequence Encoding a 155- Amino Acid Protein with Sequence Homology to Human Interleukin-1 beta and Human Interleukin-1 Receptor Antagonist The nucleotide sequence presented in Figure 5, and labeled SEQ ED NO: 4, encodes the translated amino acid sequence SEQ ED NO: 5, which is presented in Figure 6. The extended nucleotide sequence was obtained by isolating PCR products generated from pools of clones from a fetal skin cDNA library. In short, a fetal skin cDN A library was plated on ampicillin containing plates in pools of about 40,000 colonies. The colonies were recovered into LB medium and PCR was used to detect pools which contained SEQ TD NO: 2 (Figure 2). Two pools were identified. PCR using vector- and gene-specific primers amplified the 5' portion ofthe cDNA. Nested primers were used to generate sequence from the two amplified products. Laser gene™ software was used to edit and "contig" the partial sequences into a full length sequence. SEQ ED NO: 4 encodes a protein of 155 amino acids, lacking a typical hydrophobic leader peptide, suggesting that this protein is retained as a cytoplasmic molecule, similar to the cytoplasmic isoform ofthe human EL-1 Ra gene product. Figure 7 presents an amino acid alignment of SEQ DD NO: 5 with the cytoplasmic form of human EL-1 Ra (labeled "HUMELIRASIC"). The alignment reveals a high degree of homology between the two; 48% ofthe amino acids were identical and 54% represent conservative amino acid substitutions. Three residues have been proven to be critical for receptor activation by IL-1 β (marked with asterisks in Figure 7). The coπesponding residues in EL-1 Ra differ, conferring EL-1 Ra's antagonistic activity. These residues are R21, W23, and K152 for EL-1 Ra, and T9, Rl 1, and D145 for the mature IL-lβ. SEQ TD NO: 5 possesses a combination of both residues, R10 (identical to the coπesponding residue in IL-1 Ra) and K12 and D148 (similar and identical, respectively, to the coπesponding residues in IL-lβ). The overall homology and agonist/antagonist site-specific sequence homologies clearly define SEQ ED NO: 5 as a protein modulator ofthe inflammatory response. Substitute Page 7.7 EXAMPLE 7 Three Prime Extension of SEQ ID NO: 4 SEQ TD NO: 6 (Figure 8) is an extension ofthe 3' end of the nucleic acid sequence of SEQ ID NO: 4. SEQ ED NO: 6 was obtained from a fetal skin cDNA library as described above for SEQ DD NO: 4. 7.8 EXAMPLE 8 Isolation and Mapping of a Genomic Clone Corresponding to SEQ ID NOS: 1, 2, and 4 A human BAC genomic library (Research Genetics) was screened with gene-specific primers (273-D, 5'-CCCCACTGGATGGTGCTACTG-3' (SEQ ED NO: 15) which hybridizes at position 4533 to 4553 in the genomic sequence and 273-E, 5'-GGGAAGAGATAGGAAAGGTAG-3' (SEQ DD NO: 16) which hybridizes at position 4849 to 4869) using a PCR based assay. Briefly, the gene specific primers were used to amplify BAC DNAs as templates using standard PCR conditions. BACs that produce a fragment of DNA corresponding to the predicted size were pursued. BAC393-I6 was isolated and its DNA sequenced with gene-specific primers derived from SEQ DD NO 2. The sequence (16403 bases in length) is shown in Fig. 9. The IL-lRa coding sequence was found to be distributed over 5 exons. The splice donor and acceptor sites are shown below, along with intron and exon sizes. RECTIFIED SHEET (RULE 91) ISA/EP 7.9 EXAMPLE 9 Expression of SEQ ID NO: 3 in E. coli SEQ DD NO: 3 was expressed in E. coli by subcloning the entire coding region ofthe SEQ DD NO: 2 into a prokaryotic expression vector. The expression vector (pQE16) used was from the QIAexpression prokaryotic protein expression system (Qiagen). The features of this vector that make it useful for protein expression include: an efficient promoter (phage T5) to drive transcription; expression control provided by the lac operator system, which can be induced by addition of EPTG (isopropyl-β-D-thiogalactopyranoside), and an encoded His 6 tag. The latter is a stretch of 6 histidine amino acid residues which can bind very tightly to a nickel atom. The vector can be used to express a recombinant protein with a His 6 tag fused to its carboxyl terminus, allowing rapid and efficient purification using Ni-coupled affinity columns. The coding sequence of SEQ TD NO: 2 (including the start codon but excluding the stop codon) was amplified using the PCR reaction primers API (5'gaagatctatggtcctgagtggggccctg-3') (SEQ ED NO: 25) and AP2 (5'gaagatctgtcacactgctggaagtagaa-3') (SEQ ED NO: 26). Both primers have Bgl D restriction sites incoφorated at the 5' ends for cloning puφoses. The PCR fragment obtained upon amplification was restricted with Bgl D to generate staggered ends for ligating the insert into the vector. The pQE16 plasmid was digested with Bgl D and BamHI to remove a segment containing the dihydrofolate reductase coding sequence and also to generate the staggered ends compatible with those on the PCR fragment. The PCR fragment was ligated into the digested pQE16 vector to produce pl6BB-273. The ligation was transformed by electroporation into electrocompetant E. coli cells (strain Ml 5[pREP4] from Qiagen), and the transformed cells were plated on ampicillin-containing plates. Colonies were screened for the coπect insert in the proper orientation using a PCR reaction employing a gene-specific primer and a vector-specific primer. Positives were then sequenced to ensure coπect orientation and sequence. To express SEQ ED NO: 3, a colony containing a coπect recombinant clone was inoculated into L-Broth containing 100 μg/ml of ampicillin, 25 μg/ml of kanamycin, and the culture was allowed to grow overnight at 37°C. The saturated culture was then diluted 20-fold in the same medium and allowed to grow to an optical density at 600 nm of 0.5. At this point, EPTG was added to a final concentration of 1 mM to induce protein expression. The culture was allowed to grow for 5 more hours, and then the cells were harvested by centrifugation at 3000xg for 15 minutes. The resultant pellet was lysed using a mild, nonionic detergent in 20mM Tris HCl (pH 7.5) (B-PER™ Reagent from Pierce), or by sonication until the turbid cell suspension turned translucent. The lysate obtained was further purified using a nickel containing column (Ni-NTA spin column from Qiagen) under non-denaturing conditions. Briefly, the lysate was brought up to 300 mM NaCl and lOmM imidazole and was centrifuged at 700xg through the spin column to allow the His-tagged recombinant protein to bind to the nickel column. The column was then washed twice with Wash Buffer (50mM NaH 2 PO 4 , pH 8.0; 300 mM NaCl; 20mM imidazole) and was eluted with Elution Buffer (50mM NaH 2 PO 4 , ph 8.0; 300 mM NaCl; 250 mM imidazole). All the above procedures were performed at 4°C. The purified protein was checked with SDS-PAGE. A strong single band was observed, indicating a molecular weight of 16 kD, which is consistent with the predicted size of SEQ TD NO: 3. 7.10 EXAMPLE 10 Use of SEQ ID NOS: 3 and 5 7.10.1 Medical Imaging The novel Interleukin-1 receptor antagonist polypeptides ofthe invention are useful in medical imaging, e.g., imaging the site of infection, inflammation, and other sites having Interleukin-1 receptor antagonist receptor molecules. See, e.g., Kunkel et al., U.S. Pat. NO. 5,413,778. Such methods involve chemical attachment of a labeling agent, administration ofthe labeled Interleukin-1 receptor antagonist polypeptide to a subject in a pharmaceutically acceptable carrier, and imaging the labeled Interleukin-1 receptor antagonist polypeptide in vivo at the target site. 7.10.2 Pancreatitis Acute edematous, necrotizing pancreatitis is induced in adult male Swiss mice weighing more than 35 grams using caerulein— an analog of cholecystokinin. Mice are divided into four groups with three ofthe groups receiving caerulein 50 mu g/kg by intraperitoneal (EP) injection in four doses over three hours as previously described. (Murayama et al., Arch Surg 1990;125:1570-1572; Tani et al., International J Pancreatology 1987;2:337-348; Schoenberg et al., Free Radical Biology & Medicine 1992;12:515-522; Heath et al., Pancreas 1993;66:41-45; Saluja et al., Amer Physiological Society 1985: G702-G710; Manso et al., Digestive Disease and Sciences 1992;37:364-368). Group 1 is a control group (n-9) which received only EP saline injections. Group 2 (n=12) is an untreated disease control. Group 3 (n=12) received three injections (10 mg/kg/hr) starting one hour prior to induction of pancreatitis. Group 4 (n=12) received three injections (10 mg/kg/hr) starting one hour after induction of pancreatitis. After a suitable time period, all animals are euthanized, the blood collected, and the pancreata surgically excised and weighed. Serum is assayed for amylase, lipase, EL-6, and TNF levels. Each pancreas is fixed, stained, and graded histologically in a blinded fashion for interstitial edema, granulocyte infiltration, acinar vacuolization, and acinar cell. Additionally, serum levels of Interleukin-1 receptor antagonist are determined, therefore allowing comparisons between dosage, serum level, systemic cytokine response, and degree of pancreatic damage. Interleukin-6, Interleukin-1, Interleukin-1 receptor antagonist, and TNF are measured by commercially available ELISA kits (Genzyme Coφ., Boston, Mass.). All specimens are run in triplicate. Serum levels of amylase and lipase are measured on a Kodak Ectachem 700 automated analyzer (Eastman Kodak Company, Rochester, N.Y.). Histologic slides are prepared as is known in the art after rapid excision and subsequent fixation in 10% formalin. The tissues are paraffin embedded as is known in the art and then stained with Hematoxylin and Eosin in a standard fashion. These slides are examined and graded in a blinded fashion by a board certified pathologist. 7.10 3 Inhibition Of Interleukin-1 Induced Cell Proliferation Murine D10 T cells are obtained from the American Type Culture Collection (Rockville, Md.). Cells are maintained in Dulbecco's modified Eagle medium and Ham's F-12 medium (1:1) containing 10 mM HEPES buffer (pH 7.4) and 10% fetal bovine serum. All tissue culture reagents contained less than 0.25 ng/mL endotoxin as measured by the limulus amebocyte assay. Murine D10 cells, an Interleukin-1 dependent T-cell line, are used to measure Interleukin-1 mitogenic activity. Cell proliferation in the present of Interleukin-1 with and without the Interleukin-1 receptor antagonist polypeptides ofthe invention is assessed by incoφoration of ( sup 3 H) thymidine as previously described (Bakouche, O., et al. J. Immunol. 138:4249-4255, 1987). In a prefeπed embodiment, antagonists and agonist ofthe Interleukin-1 receptor antagonist polypeptides ofthe invention are identified in this assay by adding the candidate compounds with the Interleukin-1 and Interleukin-1 receptor antagonist polypeptides ofthe invention and measuring the change in cell proliferation caused by the candidate compound. 7.10.4 Inhibition Of Interleukin-1 Induced Cell Cytotoxicity Inhibition of Interleukin-1 -induced cytotoxicity is studied using an appropriate cell line, such as, for example, A375 tumor cells plated at a density of 6000 cells per well in 96-well micro titer plates. After overnight attachment, Interleukin-1 (3-300 ng/mL) is added in the presence or absence of NAA or NMA. After cells are incubated for 3 days, ( sup 3 H) thymidine is added (1 mu Ci per well) for an additional 2 hours. Cells are harvested onto glass fiber disks (PHD Cell Harvested; Cambridge Technology, Inc., Watertown, Ma.) Disks are air dried overnight, and radioactivity is determined with a Model 1900TR Scintillation Counter (Packard Instrument Division, Downers Grove, 111.) 7.10.5 Induction Of Nitrite Synthesis In Smooth Muscle Cells Aortic smooth muscle cells are cultured by explanting segments ofthe medial layer of aortas from adult male Fischer 344 rats. Aortas are removed aseptically and freed of adventitial and endothelial cells by scraping both the luminal and abluminal surfaces. Medial fragments are allowed to attach to Primaria 25-cm sup 2 tissue culture flasks (Becton-Dickinson, Lincoln Park, N.J.) which are kept moist with growth medium until cells emerged. Cultures are fed twice weekly with medium 199 containing 10% fetal bovine serum, 25 mM HEPES buffer (pH 7.4), 2 mM L-glutamine, 40 mu g/mL endothelial cell growth supplement (Biomedical Technologies, Inc., Stoughton, Mass.) and 10 mu g/ml gentamicin (GD3CO BRL, Grand Island, N.Y.). When primary cultures become confluent, they are passaged by trypsinization, and explants are discarded. For these studies, cells from passages 12-14 are seeded at 20,000 per well in 96-well plates and are used at confluence (60,000-80,000 cells per well). The cells exhibit the classic smooth muscle cell phenotype with hill and valley moφhology, and they stain positively for smooth muscle actin. Rat aortic smooth muscle cells are incubated with RPMI- 1640 medium containing 10% bovine calf serum, 25 mM HEPES buffer 7.4), 2 mM glutamine, 80 U/mL penicillin, 80 mu g/mL streptomycin, 2 mu g/mL fungizone, and Interleukin-1, IFN-gamma, and various inhibitors. At the desired times, nitrite concentration in the culture medium is measured using the standard Griess assay (Green, L., et al. Anal. Biochem. 126:131-138, 1982) adapted to a 96-well micro titer plate reader (Gross, S. S., et al. Biochem. Biophys. Res. Commun. 178:823-829, 1991). Thus, 100 uL of Griess reagent (0.5% sulfanilic acid, 0.05% naphthalenediamine, and 2.5% phosphoric acid) is added to an equal volume of culture medium, and the OD sub 550 is measured and related to nitrite concentration by reference to a standard curve. The background OD sub 550 of medium incubated in the absence of cells is subtracted from experimental values. Rat aortic smooth muscle cells are incubated with RPMI- 1640 medium containing 10% bovine calf serum, 25 mM HEPES buffer (pH 7.4), 2 mM glutamine, 80 mu g/mL penicillin, 80 mu g/mL streptomycin, 2 mu g/mL fungizone, 30 mu g/mL lipopolysaccharide (Escherichia coli 0111 :B4), and 50 U/mL IFN-y. Cells are harvested after 24 hours, and cytosol is prepared (Gross, S. S., et al. Biochem. Biophys. Res. Commun. 178:823-829, 1991). Cytosolic NO synthase activity is assayed by the Fe sup 2+ -myoglobin method described previously (Gross, S. S., et al. Biochem. Biophys. Res. Commun. 178:823-829, 1991). 7.10.6 Alloreactivity Determined By Lymph Node Weight Gain Experiments are conducted to show that systemic administration of the Interleukin-1 receptor antagonists polypeptides ofthe invention suppress a localized, T cell-dependent, immune response to alloantigen presented by allogeneic cells. Mice are injected in the footpad with iπadiated, allogeneic spleen cells. The mice are then injected in the contralateral footpad with iπadiated, syngeneic spleen cells. An alloreactive response (marked by proliferation of lymphocytes and inflammation) occurs in the footpad receiving the allogeneic cells, which can be measured by determining the increase in size and weight ofthe popliteal lymph node draining the site of antigen deposition relative to controls or by an increase in cellularity. Specific pathogen free 8-12 week old BALB/c (H-2 sup d) and C57BL/6 (H-2 sup b) mice (Jackson Laboratory, Bar Harbor, Me.) are used in this experiment. 48 BALB/c mice are divided into 16 groups, each having 3 mice (unless otherwise indicated). Each group of mice received a different mode of treatment. On day 0 the left footpads of all mice are injected intracutaneously with 107 iπadiated (2500R), allogeneic spleen cells from C57BL/6 mice in 50 μl of RPMI-1640 (Gibco) as antigen and the right contralateral footpads ofthe same mice are injected with 10 sup 7 iπadiated (2500R), syngeneic spleen cells from BALB/c mice. Seven days after antigen administration, the mice are sacrificed and the popliteal lymph nodes (PLN) are removed from the right and left popliteal fossa by surgical dissection. Lymph nodes are weighed and the results expressed as the difference (DELTA) in weight (mg) ofthe lymph node draining the site of allogeneic cell injection and the weight ofthe node draining the syngeneic cell injection site. Lymph nodes draining the syngeneic cell injection site weighed approximately 1 mg, regardless of whether they are obtained from mice treated with MSA or Interleukin-1 receptor antagonist polypeptides ofthe invention, and did not differ significantly in weight from nodes obtained from mice given no cell injection. 7.10.7 Suppression Of Organ Graft Rejection In Vivo Neonatal C57BL/6 (H-2 sup b) hearts are transplanted into the ear pinnae of adult BALB/c (H-2 sup d) recipients utilizing the method of Fulmer et al., Am. J. Anat. 1 13:273, 1963, modified as described by Trager et al., Transplantation 47:587, 1989, and Van Buren et al., Transplant. Proc. 15:2967, 1983. Survival ofthe transplanted hearts is assessed by visually inspecting the grafts for pulsatile activity. Pulsatile activity is determined by examining the ear-heart grafts of anesthetized recipients under a dissecting microscope with soft reflected light beginning on day 5 or 6 post transplant. The time of graft rejection is defined as the day after transplantation on which contractile activity ceases. Recipient mice are transplanted on day 0 and injected with either interleukin-1 receptor antagonist polypeptides ofthe invention plus MSA (mouse serum albumin, 100 ng) or with MSA alone on days 0 through 6, alternating i.p. and s.c. routes. In a second heart transplant experiment, the mice are injected with MSA alone on days 0 through 2, i.p. route only. 7.10.8 Suppression Of Inflammatory Arthritis 20 rats are divided into 4 groups, designated Groups G-J, each having 5 rats. All rats are immunized by subcutaneous injection. On day 21 following immunization with mBSA, an inflammatory arthritis response is elicited. On the same day, a negative control group is injected with a 0.2 ml volume of saline. Groups are injected with increasing amounts of Interleukin-1 receptor antagonist polypeptides ofthe invention. Interleukin-1 is injected in one group as a positive control. The diameter of the largest region ofthe treated joints is measured using a caliper on days 2, 4, 6 and 8 relative to day 0 intra-articular injection of antigen. 7.11 EXAMPLE 11 Isolation and Mapping of a Genomic Clone Corresponding to SEQ ID NO: 6 FIGS 10A-C show a genomic clone (SEQ TD NO: 8) which is an extension of the genomic sequence presented in Figure 9A-C (SEQ TD NO: 7). SEQ ED NO: 8 includes the extended sequence (three prime untranslated) shown in SEQ ED NO: 6. The isolation of this genomic clone (SEQ TD NO: 8 ) was the same as described in Example 8. The sequence is 7,605 nucleotides in length) is shown in Fig. lOA-C. The organization ofthe exons for this clone is described below. Exon Nucleotide Intronic/Exonic Range of Exon Sequences*** Exon I E * 1308-1383 ctgtagGCCTGG AAAAAGgtaagg(SEQ ID NOS: 27 & 28) Exon 1 M ** 1780-1890 cctcagGTCCTG TCTGAGgtatgc(SEQ ID NOS: 29 & 17) Exon 2 2061 -21 16 aaatagGGGAGT CTTCCGgtgagt(SEQ ID NOS: 18 & 19) Exon 3 3504-3589 tttcagAATGAA TTAAAGgttggt(SEQ ID NOS: 20 & 21) Exon 4 4777-4905 ccacagGTGAAG CTAGAGgtgaga(SEQ ID NOS: 22 & 23) Exon 5 5107-7395 cggcagCCAGTG AAAGAG(SEQ ID NO: 24) * Exon I E, exon 1 in epidermoid carcinoma cell line A431 ** Exon 1 M, exon 1 in activated macrophagc cell line THP1 ***Intronic sequences shown in lowercase, exonic sequences shown in uppercase. 7.12 EXAMPLE 12 Recombinant Protein Expression and Purification An expression vector placing the Interleukin-1 Receptor Antagonist coding sequence (SEQ TD NO: 3) without the N terminal hydrophobic sequence was placed after the His 6 tag (a stretch of 6 histidine amino acid residues) and express tags (antibody tag) in the pRSET vector (confeπing ampicillin resistance). The His 6 tag fused to its amino terminus of a recombinant protein allows rapid and efficient purification using Ni-coupled affinity columns. This construct was transformed into E. coli (BL-21 with the pLYS plasmid confeπing chloramphenicol resistance) and expression was induced using EPTG (1 mM final). Bacterial pellet was suspended in 50mM Tris pH.7.5. Sonic dismembrator was employed to lyse cells in the presence of 1 mg/ml of lysozyme (10ml of buffer per gram of wet cells). Cell debris was removed by centrifugation. Imidazole was added at 10 mM final concentration with 100 mM NaCl. The extract was loaded on a Nickel chelate column. The protein was eluted off the column with a linear gradient of imidazole from 50 mM to 300 mM. After the peak was collected, it was desalted on a sephadex G-25 column into 20 mM sodium phosphate buffer. Protein was loaded onto a Q-sepharose column and eluted off the gradient from 0-350 mM NaCl. The final recombinant protein was filter sterilized and stored at -20°C. 7.13 EXAMPLE 13 Binding of the Interleukin-1 Hyl Receptor Antagonist to the Interleukin-1 Receptor A cell binding assay was carried out to demonstrate that Interleukin- IHyl Receptor Antagonist of the invention binds to the Interleukin-1 receptor. Briefly, cell binding ofthe recombinant protein (see Example 12) with and without the presence of 100 fold greater amounts of non tagged Interleukin-1 Beta (IL-lβ) ligand was analyzed by using fluorescent antibodies specific for the express tag in the Interleukin-1 Hyl Receptor Antagonist recombinant protein on the fluorescent activated cell sorter (FACS). In each reaction, 10 6 cells NHDF (normal human dermal fibroblasts) were resuspended in lOOul of FACS buffer (distilled PBS and 3% calf serum and 0.01% azide). Cell binding was done by adding 5 nM recombinant Interleukin-1 Hyl Receptor Antagonist in 100 μl cell suspension and as a competition in one reaction,. 500nM of recombinant IL-1 β was also added. The cells were incubated on ice for 1 hr. The cells were pelleted, 200 μl of 0.2 mM BS3 (crosslinker) was added, and the cells were kept on ice for 30 min. Next, 10 μl 1 M Tris pH 7.5 was added and the cells were incubated for 15 minutes on ice. The cells were pelleted, washed 1 time in FACS buffer, resuspended in 100 μl volume of FACS buffer and 2 μl primary antibody (anti-express tag antibody lmg/ml) was added, and incubated on ice for 30 min. The cells were pelleted, washed with FACS buffer, and resuspended in FACS buffer (100 μl volume). The secondary antibody (phycoerythrin conjugated) 2ul of anti-mouse Ig (lmg/ml) was added and the cells were incubated for 30 minutes on ice. The cells were again pelleted, washed two times with FACS buffer, resuspended in 0.5 ml FACS buffer and analyzed on FACS. A shift in the fluorescence was observed in the cells treated with the recombinant tagged Interleukin- IHyl Receptor Antagonist. This binding was shown to be specific, as is was competed off with the non-tagged EL-1 β protein. These results indicate binding ofthe Interleukin-1 Hyl Receptor Antagonist protein of the invention to the EL-1 receptor. The assay was repeated using unlabeled IL-1 Hyl Receptor Antagonist (IL-1 Hyl RA) as the ligand. A shift in fluorescence was observed for the cells treated with the recombinant tagged IL-1 Hyl. This binding was specific, as binding was decreased in the presence ofthe non-tagged IL-1 Hyl RA protein. These results confirmed binding ofthe EL-1 Hyl protein of the invention to the IL-1 receptor. 7.14 EXAMPLE 14 Confirmation of IL-1 antagonist activity IL-1 antagonist activity was determined using a prostaglandin E 2 (PGE 2 ) based assay as follows. NHDF cells were plated at 2 X IO 4 cells per well in a 96-well plate 24 hours before the assay. The cells were then treated with 25 pg/ml recombinant human IL-lβ (R&D Systems) for 16 hours at 37°C in a 5% CO 2 incubator. To study the inhibition of IL-lβ stimulated PGE 2 release by IL-lHyl, the cells were pretreated with different amounts of EL-lHyl for two hours before the addition of EL-lβ. The supernatants were then collected and cell debris was removed by centrifugation. The amount of PGE 2 in the supernatants was determined by ELISA using the PGE 2 assay system (R&D Systems) according to the manufacturer's directions. When NHDF cells were treated with IL-lHyl alone, no PGE 2 activity was measured. To determine whether IL-lHyl could inhibit IL-lβ induced PGE 2 production, the cells were pretreated with different concentrations of EL- IHyl before stimulation with IL-lβ. EL-lHyl was able to inhibit EL-lβ induced PGE 2 production in a dose dependent fashion as shown in Figure 11. These results indicate that EL-lHyl acts in a manner similar to EL-lra in vitro, indicating that they have overlapping functions. The assay may alternatively be conducted with CCD 1098 human fibroblast cells (ATCC Accession No. CRL2127) as follows. Approximately 2 X IO 4 cells per well were seeded in 96 well plate the day before cell stimulation. On the day of stimulation, cells were washed once with fresh medium and replated with 200 μl fresh medium in each well. The cells were stimulated with IL-lβ (at a final concentration of 1 ng/ml) or with the cytokine of interest alone. To test PGE 2 inhibition, different concentrations of EL-1 Hyl or EL-lra were added to the wells together with IL-lβ. After 16 hours of cell stimulation, the culture plate was spun for 5 minutes at 4000 φm to remove cell debris. 100 μl supernatant was removed to test for the presence of PGE 2 using PGE 2 assay kit manufactured by R & D system. The assay was caπied out according to manufacturer's instruction. Results of this assay confirmed that IL-1 Hyl partially inhibited EL-lβ stimulated PGE 2 production in a dose-dependent manner (about 40-60% inhibition at 1000-fold excess). It is possible that more highly purified preparations of IL-1 Hyl may show complete inhibition in this assay. In comparison, EL-lra completely PGE 2 inhibited production at 100-fold excess. 7.15 EXAMPLE 15 Inhibition of IL-lβ Induced IL-6 Production Inhibition of Interleukin- lβ induced IL-6 production was studied using human endothelial cells from umbilical vein (Huvec). Huvec cells were seeded at 2 X IO 4 cells per well in a 96-well plate the day before cell stimulation. On the day of stimulation, cells were washed once with fresh medium (F12 medium with 100 μg/ml heparin, 50 μg/ml endothelial growth supplement and 10% fetal bovine serum) and replated with 200 μl of fresh medium [without supplements] in each well. The Huvec cells were then stimulated with 100 pg/ml (final volume) of IL-lβ. Although this assay was done with EL-lβ, any cytokine of interest can be used. To test IL-6 inhibition, different concentrations of IL-lHyl (ranging from lOx to lOOOx the concentration of IL-lβ) or EL-lra (ranging from lOx to lOOOx IL-lβ concentration) were added to the wells with the EL- lβ. After 16 hours of cell stimulation, the culture plate was spun for five minutes at 4000 φm to remove cell debris. 100 μl ofthe supernatant was removed to test for the presence of IL-6 using a human EL-6 immunoassay kit (R&D Systems) according to the manufacturer's instructions. IL-lHyl partially inhibited IL-lβ-stimulated EL-6 production in a dose- dependent manner. In view ofthe fact that IL-6 blocks production of tumor necrosis factor (TNF), a pro-inflammatory cytokine, the fact that EL-lHyl only partially inhibits of IL-6 production by ELI -Hyl may be beneficial in the treatment of inflammatory disease states with ELI -Hyl due to reduced side effects. It is possible that more highly purified preparations of IL-1 Hyl may show complete inhibition in this assay. 7.16 EXAMPLE 16 Determination of Molecular Mass of IL-lHyl Expressed in Human Cells To determine the molecular mass of EL-lHyl expressed in human cells, the human cell line THP-1 was used in experiments designed to detect the presence of EL- IHyl. As described in Mulero, et al., BBRC 263(3):702-706 (1999), THP-1 cells express moderate levels of EL-lHyl when differentiated with phorbol ester (PMA) and subsequently stimulated with lipopolysaccharide (LPS). Briefly, THP-1 cells (ATCC) were grown to confluency under conditions and media described in Mulero et al., supra, and then treated with 200 ng/ml of PMA (Sigma) and incubated at 37°C for 48 hours. The cells were then subjected to 2 μg/ml of LPS (Sigma) and incubated at 37°C for 24 hours. The cells and media were then harvested in the presence of protease inhibitors (pepstatin, leupeptin and aprotinin; Sigma). After harvesting, the cells were lysed in a PLB lysis buffer (Promega). The media was processed by centrifugation to remove cell debris and concentrated twenty fold using centriprep (Amicon). Recombinant IL-lHyl was also produced as follows. The plasmid pYZ5829 (T7 promoter) was constructed by digesting EL-lHyl cDNA with Ndel and BamHI and cloning the resulting fragment in a Ndel-BamHI digested pRSET B vector (Invitrogen). This construct contains the 5' most methionine codon of SEQ ED NO: 4. E. coli BL21plysE (Invitrogen) cells were transformed with this vector and cultured in 2L flasks (for yields of about 2 g wet cell paste per liter of culture). The cells were disrupted in 10 ml per g wet cell paste 20mM sodium phosphate, pH 7.5, using an Emulsiflex homogenizer. 5 M acetic acid was added to titrate the pH to 4.8, thus precipitating E. coli proteins, and the cell suspension was centrifuged. The IL-lHyl remains in the supernatant. 5M acetic acid was added to the supernatant to titrate to pH 4.5, precipitating additional proteins, and the resulting suspension was centrifuged again. The resulting supernatant was then loaded onto an SP-Sepharose cation exchange column (Pharmacia) at pH 4.5 The EL-lHyl was eluted with a 0 to 250 mM NaCl linear gradient (10 x column volume), giving >90% pure protein. The protein- containing fractions were pooled, titrated to pH 8.0 with 5M NaOH, and 1M Tris was added to 50mM. Ammonium sulfate was added to 0.75M and the pool was loaded onto a butyl-Sepharose column (Pharmacia). IL-lHyl was eluted with a reverse salt gradient (20 column volumes). The protein was concentrated to 5-10 mg/ml and desalted by buffer exchange into 20 mM sodium phosphate buffer at pH 7 on Sephadex G-25 (Pharmacia). The resulting solution was loaded onto a Q-Sepharose (Pharmacia) anion exchange column, and EL-lHyl was collected in the flow through. NaCl was added to 0.1M, the protein solution was concentrated to 25 mg/ml and stored at -70°C. The THP-1 and the bacterially produced recombinant IL-lHyl protein preparations described above were loaded on an SDS-PAGE gel and transfeπed to a filter (Immobilon-P, Millipore) by Western blotting. The filter was then probed with polyclonal anti-IL-lHyl antibody specific for IL-lHyl prepared by immunizing rabbits with IL-lHyl peptide: RLTQLPENGGWNA using conventional methods [see, e.g., Harlow et al., "Antibodies: A Laboratory Manual", Cold Spring Harbor Laboratories, Cold Spring Harbor, NY (1998)] and control preimmune serum from the immunized rabbits. No EL-lHyl was detected in the media alone. A 17kDa band was detected in the lane loaded with recombinant IL-lHyl protein prepared from E. coli (translated from the 5' most initiating methionine codon). Two bands were detected in the THP-1 cell lysate preparation: a faint band that coπesponded to the same molecular mass as the recombinant bacterially expressed EL-lHyl, representing a molecular mass of approximately 17 kDa; and a predominant band representing a molecular mass of approximately 15.5 kDa. The presence ofthe approximately 15.5 kDa band suggested that the naturally occurring L-lHyl protein may be processed in mammalian cells. In addition, the mature putative processed form is significantly smaller than the 17 kDa form expressed from the initiating methionine codon commencing at nucleotide position 73 of SEQ TD NO: 4 (coπesponding to amino acid position 1 of SEQ ED NO: 5). It is possible that the -15.5 kDa IL-lHyl is the product of an alternative start methionine codon commencing at nucleotide position 103 of SEQ TD NO: 4 (coπesponding to amino acid position 11 of SEQ ED NO: 5), which would give a predicted molecular mass of about 16 kDa. It is also possible that the -15.5 kDa EL- lHyl is the product of proteolytic processing after the aspartic acid at amino acid position 13 of SEQ TD NO: 5. SEQ ED NO: 5 is the deduced amino acid sequence coπesponding to an open reading frame identified in SEQ ED NO: 4. The invention contemplates polypeptide fragments of SEQ ED NO: 5 (either C-terminal or N-terminal fragments) having a molecular mass as determined by SDS-PAGE of about 16 kDa or less, preferably about 15.5 kDa. The invention also specifically contemplates N-terminally truncated fragments of SEQ DD NO: 4 that commence at either amino acid residue 11 or 14, as well as polynucleotides encoding such N-terminally truncated fragments. EXAMPLE 17 IL-1 Hyl expression in activated THP-1 cells THP-1 cells were activated with PMA and LPS exactly as described above in Example 16; cells and media were harvested after an additional 24 hours in serum-free media, and cell lysates were prepared as described above. Control, non-activated THP- 1 cells were also prepared by culturing cells for an equal amount of time in media without PMA or LPS, and cell lysates were prepared as described above. Western blotting detected IL-lHyl protein in the cell lysate from activated THP-1 cells, while only a very little amount of IL-lHyl was detected in the cell lysate from non-activated cells. These results indicate that IL-lHyl protein expression is upregulated in activated THP-1 cells. EXAMPLE 18 Detection of IL-lHyl protein expression in human tissues by immunohistochemistry Slides of three different human tissue samples (tonsil, skin, and allergic nasal polyps from patients suffering from chronic allergy conditions) were stained with the rabbit polyclonal anti-ELl Hyl antibody prepared described above in Example 16. Anti-IL-1 Hyl antibody binding was detected by biotinylated goat-anti -rabbit secondary antibody followed by streptavidin-HRP detection. To visually detect staining, the slides were treated with the chromogen 3,3'-diaminobenzidine (DAB; a brown stain) and counter stained with hematoxylin (blue nuclear stain). A negative control was stained in the same way in the absence of anti-IL-1 Hyl antibody. In addition, double label staining was done as follows (see Myers, J.A., Mehta, P., Hunter, A.W., Berstein, S.A., and Erickson, P.A., "Automated Double-Label: Immunohistochemistry", Journal of Surgical Pathology, 1 :105-113 (1995). Myers, J.A., D'Andrea, M.R., Hunter, A.W., Mehta, P., Berstein, S.A., and Erickson, P.A., "Automated Double-Label: In Situ Hybridization and Immunohistochemistry", Journal of Surgical Pathology, 1:191-203 (1995)) The anti-ILlHyl primary antibody staining was done as described immediately above except that fast red was used as the chromogen (a red stain). A second primary antibody described below (specific for cell phenotype markers) was detected using a biotinylated secondary antibody followed by streptavidin-HRP. DAB was used as the chromogen (brown). The slides were counter stained with hematoxylin (a blue nuclear stain) and were visualized on a light microscope. Results showed that the EL-lHyl protein was located in the cytoplasm of skin epithelial cells. In the tonsil, there was positive staining in scattered cells in some germinal centers and epithelial crypts. There was no staining in T-cells (CD45RO marker), B cells (CD20 marker), macrophages (CD68 marker), or in monocytes, macrophages and Langerhans cells (CD 14 marker). Sections ofthe allergic nasal polyps were double label stained with antibodies against the EL-1 Hyl protein and IgE, and were double label stained with anti-Il-1 Hyl and anti-CD138. Tissue sections were then reacted with secondary antibodies and streptavidin-HRP, and treated with the chromogen 3-amino-9-ethylcarbazole (AEC,. red stain). In the allergic nasal polyps, IL-1 Hyl protein is expressed in plasma cells (CD138 positive) that are IgE negative. These results suggest that IL-1 Hyl plays a role in modulating allergic reactions in the allergic nasal polyps. Therefore, IL-1 Hyl or antagonists of its activity (e.g. antibodies) may be useful in the treatment of allergic reactions, such as allergic rhinitis and asthma. Effects of IL-1 Hyl or antagonists thereof can be confirmed in any ofthe allergy animal models described herein or known in the art. Serial section immunostaining was also performed on human tissues, including normal nasal tissue, chronic infected nasal polyps, allergic nasal polyps, normal lungs, and lung tissue from patients with chronic bronchitis due to chronic infection. Tissue sections were reacted with rabbit polyclonal anti-ILl-Hyl antibody prepared as described in Example 16 above. Anti-IL-1 Hyl antibody binding was detected by biotinylated goat-anti-rabbit secondary antibody followed by streptavidin-AP detection. To visually detect staining, the slides were treated with the chromagen, (Fast Red) and counter stained with hematoxylin (blue nuclear stain). The results demonstrate that allergic nasal polyps and chronically infected nasal polyps had many more cells expressing IL-1 Hyl protein than the normal nasal polyps. Furthermore, the majority ofthe EL-1 Hyl expressing cells are IgA-producing plasma cells. In the lung tissues tested, chronic bronchitis lung tissues had many more IL-1 Hyl expressing cells than normal lung tissue. The IL-1 Hyl expressing cells included plasma cells, macrophages and bronchial epithelium cells; expression was highest in the plasma cells. These results suggest that IL-1 Hyl expressing cells are recruited to the site of allergic, infected or inflamed tissue and play a role in modulating inflammation due to allergy and/or acute or chronic infection. Additional experiments were conducted to verify these results. Biopsy samples from patients with normal nasal tissue, allergic nasal polyps, chronic infected nasal polyps, normal lung and chronically infected lung were tested for IL-1 Hyl expressing cells (HLC) as described above. In this study, there were more IL-1 Hyl expressing cells and eosinophils in allergic nasal polyps than in normal nasal (p = 0.074 for both cell populations) and chronically infected nasal tissues (p = 0.07 for HLC, p = 0.08 for eosinophils). There were also more IL-1 Hyl expressing cells and eosinophils in chronic lung tissue than in normal lung tissue (p = 0.128 for HLC, p = 0.197 for eosinophils), although the difference was less apparent for the eosinophils. With respect to allergic nasal polyp and chronically infected lung tissues, these results were consistent with results observed in the first experiments. The values of probability (p value based on the Students T test of matched samples), while ranging from 0.07 to 1.97, were not significantly different due to the low sample size (n = 3). Expanding the study will yield more definitive statistical differences. EXAMPLE 19 Detection of IL-lHyl protein expression in human tissues by in-situ hybridization using DNA probe To determine tissue and cell types that express IL-lHyl mRNA, a 985 nucleotide EcoRI and HindDI fragment (which included the complete IL-1 Hyl open reading frame) ofthe RTA00000273.C.07 clone from a fetal liver-spleen cDNA library was used as a probe on a panel of sectioned human tissues. The probe was labeled using the digoxigenin labeling kit supplied by Boehringer-Mannheim using manufacturer's directions. Automated in-situ hybridization was performed by QualTek Molecular Labs (see Myers, et al., J. Surg. Path., 1 :191-203 (1995). All tissues were fixed in 10% neutral buffered formalin, paraffin-embedded and cut into 4 μm sections. Cells in skin, brain and tonsil specifically hybridized to the IL-lHyl probe. A strong signal was detected in the basal layer of the skin epithelia. Sporadic cells in the tonsil also produced a signal with strong intensity. Brain cerebellum tissue provides evidence of expression in presumed infiltrating leukocytes found suπounding an artery in the white matter. A different section of cerebellum from the same individual exhibits staining of presumed glial cells located in the molecular layer. EXAMPLE 20 Detection of IL-lHyl mRNA expression in human tissues by in-situ hybridization using Riboprobe The following three pairs of riboprobes were labeled using the digoxigenin labeling kit from Boehringer-Mannheim following manufacturer's directions. Hyl -RNA1 -5 5 '-CACAGCTCCCGCCAGGAGAA-3 ' Hyl-RNAl-3 5'-GGGACCACGCTGATCTCTTC-3' Hyl-RNA2-5 5'-AGCTTCCCGAGAATGGTGGC-3' Hyl -RNA2-3 5 '-GTGGTC AGGTGCCC ACTAAG-3 ' Hyl -RNA3-5 5 '-CTGGGTAAGGAACTTAAAGAAC-3 ' Hyl-RNA3-3 5'-TCTTAACTAACTACATCTGCA-3' Serial sections of human normal tonsil were exposed to the DIG-labeled IL-1 Hyl riboprobes and to antibodies for the following cell phenotype marker proteins: CD20 (B cells), K167 (proliferating cells) CD3 (T cells), CD la (dendritic and langerhans cells), CD 14 (monocytes, macrophages and langerhans cells), CD68 (macrophages), LN5 (macrophages, mantle zone cells and histocytes) and epithelial membrane antigen. Staining was done as described above. The IL-1 Hyl gene was expressed in scattered cells in some germinal centers (in the area where B cells are activated) and in the epithelial crypts. It was not clear whether it is expressed in macrophages or a subset of activated B cells. EXAMPLE 21 Induction of IL-13 by IL-lHyl The ability of IL-1 Hyl to affect production of IL-13 was examined as follows. One day prior to the experiment, normal human bronchial epithelial cells (NHBE) (Clonetics, San Diego, CA) or normal human small airway epithelial cells (SAEC) (Clonetics) were seeded at 8 x IO 4 cell/ml in one ml growth media (Clonetics). On the day ofthe experiment, the cells were stimulated with either II- 1 Hyl (1 μg/ml final concentration) or IL-lβ (1 ng/ml final concentration). After 20 hours incubation at 37°C in 5% CO 2 , cell supernatants were collected. Cell debris was removed by centrifugation and the amount of IL-13 in the supernatant was quantitated by using an IL-13 ELISA kit (Biosource International) according to the manufacturer's suggested protocol. Results indicated that ILl-Hyl was able to induce IL-13 production in both cell types tested while IL-lβ induced IL-13 production only in the NHBE cells at the concentration tested. In SAEC cells, IL-1 Hyl induced IL-13 production 110-fold over background, and in NHBE cells, IL-1 Hyl induced IL-13 production 60-fold. In NHBE cells, EL-lβ induced IL-13 production by the same 60-fold over background: These results, taken in combination with previous results from IL-6 and PGE 2 assays described above, suggests that an inhibitory effect of IL-1 Hyl on EL-lβ activity may be indirect in that an increase in EL- 13 production in turn decreases EL-lβ synthesis. EXAMPLE 22 Inhibition of IL-18 activity by IL-1 Hyl The following experiment evaluated the ability of IL-1 Hyl to inhibit EL-18 activity, as measured by induction of EFN-γ. Human lymphocytes (PBMC) were obtained by Ficoll-Hypaque density gradient separation of peripheral blood from healthy volunteer donors. Immediately after isolation, the PBMC were washed two times with growth media, containing RPMI 1640-10% fetal bovine serum., and 3 x 10 5 cells/well were seeded in a 96 well plate. The cells were stimulated by adding anti- CD3 antibody ® & D Systems, Minneapolis, MN) to all ofthe samples at a final concentration of 0.5 μg/ml. At the time of stimulation, the wells were also treated with a 100 ng/ml human recombinant IL-18 (R&D Systems) for 36 hours at 37°C at 5% CO 2 . A portion of the wells on each plate (triplicates) were untreated to served as a measure of background levels of EFN produced by stimulated PBMC cells. IL-18 treatment causes the PBMC cells to increase production of EFN-γ relative to the background levels. To assay for IL-1 Hyl inhibition of IL-18 stimulated EFNγ production, lOOx to lOOOx fold concentration of EL-1 Hyl (relative to EL-18 concentration) was added to wells together with IL-18 at the time of stimulation. After 36 hours of cell stimulation, the culture plate was centrifuged for 5 minutes at 4000 φm to remove cell debris. The supernatant was assayed for EFNγ using the Qantikine IFNγ ELISA kit ® & D Systems) according to the manufacturer's suggested protocol. Results indicated that IL-18 alone stimulated EFNγ production and that IL-1 Hyl inhibited the IL-18 stimulation in a dose dependent fashion, with complete inhibition observed at 500-fold to 1000-fold excess IL-1 Hyl. In order to assess the mechanism by which IL-1 Hyl reduced IFNγ production, the following assay was caπied out. Human lymphocytes (PBMC) were obtained, washed, seeded, stimulated with anti-CD3 and treated with a final concentration of 100 ng/ml EL-18 ® & D Systems) as described above. Several blocking antibodies were then used to test inhibition of EFNγ production, including anti-IL 18 receptor antibody, anti-Receptor accessory protein polyclonal antisera, anti-ELl receptor type I antibody and anti-ELl receptor type D antibody (all obtained from R & D Systems, Minneapolis, MN). Different amounts of each antibody were added to the wells with IL-18, and after 36 hours of cell stimulation, the culture plate was centrifuged for 5 min at 4000 φm to remove cell debris. The supernatant was assayed for EFNγ using the Qantikine EFNγ ELISA kit ® & D Systems) according to manufacturer's instructions. In the absence of an antibody, EL-18 stimulated EFNγ production relative to background levels as observed above. However, anti-ELl 8 receptor antibody, anti- accessory protein antibody and anti-IL-1 receptor type I, but not type π, antibody inhibited IL-18 induced EFNγ production. These results indicate that compounds which antagonize the action ofthe EL-1 receptor inhibit IL-18 activity as measured by induction of EFNγ production. EXAMPLE 22 Binding of IL-1 Hyl to the Interleukin-1 Receptor A cell binding assay was caπied out to determine if IL-1 Hyl ofthe invention binds to the interleukin-1 (IL-1) receptor. Briefly, fluorescent activated cell sorting (FACS) was used to measure cell binding ofthe recombinant protein (see Example 12) in the presence and absence of a 100-fold greater amount of unlabeled IL-1 receptor antagonist (IL-1 RA) ligand using fluorescent antibodies specific for the express tag in the IL-1 Hyl recombinant protein. In each reaction, IO 6 cells normal human dermal fibroblasts (NHDF ) were suspended in 100 μl of FACS buffer (containing distilled PBS, 3% calf serum and 0.01% azide). Cell binding reactions included 5 nM recombinant IL-1 Hyl in 100 μl cell suspension; binding competition in one reaction included 500 nM of recombinant EL-1 RA. The cells were incubated on ice for one hr. The cells were pelleted by centrifugation, 200 μl of 0.2 mM BS3 (crossliner) was added, and the cells were kept on ice for 30 min. Next, 10 μl 1 M Tris pH 7.5 was added and the cells were incubated for 15 minutes on ice. The cells were pelleted by centrifugation, washed one time in FACS buffer, resuspended in 100 μl volume of FACS buffer, 2 μl primary antibody (anti-express tag antibody lmg/ml) was added, and incubation continued on ice for an additional 30 min. The cells were pelleted by centrifugation, washed with FACS buffer, and resuspended in FACS buffer (100 μl volume). The secondary antibody (phycoerythrin-conjugated), 2 μl of anti-mouse Ig (lmg/ml), was added and the cells were incubated for 30 minutes on ice. The cells were again pelleted by centrifugation, washed two times with FACS buffer, resuspended in 0.5 ml FACS buffer and analyzed on FACS. A shift in the fluorescence was observed for the cells treated with the recombinant tagged IL-1 Hyl. This binding was specific, as binding was decreased in the presence ofthe non-tagged IL-1 RA protein. These results indicate binding ofthe IL-1 Hyl protein ofthe invention to the IL-1 receptor. EXAMPLE 23 Expression of IL-1 Hyl in Skin Fibroblast Cells Western blot analysis was performed to detect IL-1 Hyl polypeptide expression in human skin fibroblasts. Normal human foreskin fibroblast cells (ATCC No. CCD 1098) were lysed with PLB lysis buffer, the lysate was separated on a SDS polyacrylamide gel, and the resolved proteins were transfeπed to a filter as described in Example 16. The filter was probed with a polyclonal anti-IL-1 Hyl antibody specific for IL-1 Hyl as prepared as described in Example 16. Results indicated that IL-1 Hyl polypeptide was detectable in human foreskin fibroblasts. EXAMPLE 24 Induction of ICAM-1 Expression by IL-1 Hyl Airway inflammation is characterized by a local influx of neutrophils and increased expression of adhesion molecules such as ICAM-1. To determine if IL-1 Hyl plays a role in airway inflammation, the effect of EL-1 Hyl on ICAM-1 expression small airway epithelial cells was examined according to the method described by Tosi et al. (Am. J. Resip. Cell. Mol. Biol., 7: 214-221, 1992). Small airway epithelial cells (SAEC) were obtained from Clonetics (San Diego, CA) and maintained in SAGM media (Clonetics) according to the supplier's instructions. SAEC cells were seeded at 3xl0 5 cells per 60 mm precoated dish. The 60 mm dishes were precoated with a mixture of 10 μg/ml fibronectin (Sigma, St. Louis, MO), 30 μg/ml Collagen (commercially known as Vitogen 100, Cohesion, Palo Alto, CA), and 10 μg/ml bovine serum albulmin (Sigma). Twenty four hours after seeding, the cells were washed once with growth media and then treated (i.e., stimulated) with IL-lβ at 1 ng/ml and/or IL-1 Hyl at 10-fold, 100-fold, 1000-fold etc, concentrations for 24 hours. IL-lβ and IL-1 Hyl were added separately or together as indicated. After the 24 hour incubation, the cells were washed with PBS, treated with 0.5% trypsin, and resuspended in 0.1 ml FACS buffer (3% fetal bovine serum/0.01% azide/PBS). The cells were then incubated with anti- ICAM-1 antibody conjugated with R-phycoeryphrin (PE) (Pharmingen) for 30 minutes. [WHAT IS PE?] Subsequently, the cells were washed and resuspended in 25 ml FACS buffer for analysis on a fluorescent activated cell sorter (as described in Example 13). The FACS analysis indicated that treatment with IL-1 β increased ICAM-lby 130% expression and that IL-1 Hyl synergized with D_,-lβ to further increase ICAM-1 expression. The presence of ten-fold excess of IL-1 Hyl together with IL-lβ increased expression of ICAM-1 expression by 30-40% as compared to IL-lβ stimulation alone. Stimulation with IL-1 Hyl alone, however, had variable effects on ICAM-1 expression. EXAMPLE 25 Determination of the IL-1 Hyl Mouse Genomic Sequence A BAC clone containing the mouse IL-1 Hyl gene was isolated by Southern hybridization using a human IL-1 Hyl cDNA clone. The IL-1 Hyl mouse genomic sequence was obtained by sequencing the BAC clone using standard methods and is set forth as SEQ TD NO: 31. The predicted mouse IL-1 Hy 1 cDNA sequence is 465 nucleotides (SEQ ED NO: 32) and encodes a 155 amino acid polypeptide. The deduced amino acid sequence is set forth as SEQ ED NO: 33). Comparison ofthe mouse and human EL-1 Hyl amino acid sequences indicated a 91% homology. EXAMPLE 26 Animal Studies with IL-1 Hyl A. Tolerance and Toxicity Studies The maximun tolerated dose (MTD) and acute toxicity of IL-1 Hyl polypeptide was determined in mice. Recombinant human IL-1 Hyl was expressed in E.coli. and purified to homogeneity as described above. The concentration of purified IL-1 Hyl was 24.4 mg/ml and each dose was administered in a 0.2 ml volume of 100 mM sodium chloride and 20 mM sodium phosphate pH 7.0. For the MTD study, three outbred mice (CDI) weighing approximately 30 g received an initial intravenous dose (150 mg kg) ofthe IL-1 Hyl formulation via the tail vein. These mice were observed for several hours and again the next morning and did not exhibit any clinical signs. For the acute toxicity study, four groups of six outbred mice, weighing approximately 30 g, each received a single intravenous dose of IL-1 Hyl via the tail vein. Each group received a different dose of IL-1 Hyl, (vehicle alone, 3.75 mg/kg, 37.5 mg/kg, 150 mg/kg) and were observed daily for seven days. The mice did not exhibit any unusual clinical signs. On day 7, the mice were euthanized and gross necropsy did not indicate any abnormal findings. These results indicated that EL-1 Hyl appeared to be well tolerated in mice at a dose of 150 mg/kg. B. Effect of IL-1 Hyl Polypeptide on Serum Corticosterone Level Stimulated by EL- lβ The effect IL-1 Hyl on EL-lβ stimulated corticosterone levels in mice was investigated to determine EL-1 Hyl action in vivo. Groups of three mice each received a single intravenous dose (500 μg/mouse) of recombinant IL-1 Hyl polypeptide or vehicle alone. Thirty minutes after the initial injection, each mouse received a dose of EL-lβ (250 ng/mouse; R&D Systems) or vehicle alone injected subcutaneously. All the mice were terminally bled three hours after the subcutaneous injection. Serum levels of corticosterone were determined using an RIA kit (ICN Biochemicals) according to the manufacturer's suggested protocol, method described in Carter et al. (Nature 344: 633-637). The mice injected with vehicle alone showed no increase in corticosterone serum levels and determined the baseline concentration to be 220.33 ng/ml. injection of EL-1 β elevated the serum corticosterone levels to 615.06 ng/ml. Injection of IL-1 Hyl prior to IL-lβ treatment, however, reduced IL-lβ stimulated corticosterone levels to 459.22 ng/ml. These results indicate that IL-1 Hyl polypeptide inhibited EL-lβ induced activity in vivo and that at least one ofthe in vivo functions of EL-1 Hyl is to antagonize IL-1 β. The present invention is not to be limited in scope by the exemplified embodiments which are intended as illustrations of single aspects ofthe invention, and compositions and methods which are functionally equivalent are within the scope of the invention. Indeed, numerous modifications and variations in the practice ofthe invention are expected to occur to those skilled in the art upon consideration ofthe present prefeπed embodiments. Consequently, the only limitations which should be placed upon the scope ofthe invention are those which appear in the appended claims. All references cited within the body ofthe instant specification are hereby incoφorated by reference in their entirety.

Claims: WHAT IS CLAIMED IS: 1. An isolated polynucleotide comprising: (a) a nucleotide sequence of SEQ DD NO: 1 ; (b) a nucleotide sequence of SEQ ED NO: 2; (c) a nucleotide sequence of SEQ DD NO: 4; (d) a nucleotide sequence of SEQ DD NO: 6; (e) a nucleotide sequence of SEQ DD NO: 7; (f) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence encoded by the cDNA insert of clone pIL-lHy273; (g) a nucleotide sequence comprising the full length protein coding sequence of the cDNA insert of clone pIL-lHy273; (h) a nucleotide sequence comprising the mature protein coding sequence of the cDNA insert of clone pIL-lHy273; (i) the nucleotide sequence ofthe cDNA insert of clone pIL-lHy273; (j) a nucleotide sequence encoding the full length protein sequence of SEQ DD NOS: 3, or 5; (k) a nucleotide sequence encoding the mature protein sequence of SEQ DD NOS: 3, or 5; or (1) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence of SEQ DD NOS: 3, or 5. 2. An isolated polynucleotide which hybridizes to the complement ofthe polynucleotide of Claim 1 under stringent hybridization conditions. 3. An isolated polynucleotide which comprises the complement ofthe polynucleotide of Claim 1. 4. A vector comprising the isolated polynucleotide of Claim 1. 5. An expression vector comprising the isolated polynucleotide of Claim 6. A host cell genetically engineered to contain the polynucleotide of Claim 1. 7. A host cell genetically engineered to contain the polynucleotide of Claim 1 in operative association with a regulatory sequence that controls expression of the polynucleotide in the host cell. 8. An isolated polypeptide comprising: (a) an amino acid sequence of SEQ DD NOS: 3, or 5; (b) an amino acid sequence encoded by the cDNA insert of clone pIL-lHy273; (c) the amino acid sequence comprising the full length protein encoded by the cDNA insert of clone pIL-lHy273; or (d) a polypeptide comprising the mature protein encoded by the cDNA insert of clone pEL-lHy273. 9. A composition comprising the polypeptide of Claim 8 and a carrier. 10. An antibody directed against the polypeptide of Claim 8. 11. A method for detecting a polynucleotide of Claim 1 in a sample, comprising: a) contacting the sample with a compound that binds to and forms a complex with the polynucleotide for a period sufficient to form the complex; and b) detecting the complex, so that if a complex is detected, a polynucleotide of Claim 1 is detected. 12. A method for detecting a polynucleotide of Claim 1 in a sample, comprising: a) contacting the sample under stringent hybridization conditions with nucleic acid primers that anneal to a polynucleotide of Claim 1 under such conditions; and b) amplifying the polynucleotides of Claim 1 so that if a polynucleotide is amplified, a polynucleotide of Claim 1 is detected. 13. The method of Claim 12, wherein the polynucleotide is an RNA molecule that encodes a polypeptide of Claim 8, and the method further comprises reverse transcribing an annealed RNA molecule into a cDNA polynucleotide. 14. A method for detecting a polypeptide of Claim 8 in a sample, comprising: a) contacting the sample with a compound that binds to and forms a complex with the polypeptide for a period sufficient to form the complex; and b) detecting the complex, so that if a complex is detected, a polypeptide of Claim 8 is detected. 15. A method for identifying a compound that binds to a polypeptide of Claim 8, comprising: a) contacting a compound with a polypeptide of Claim 8 for a time sufficient to form a polypeptide/compound complex; and b) detecting the complex, so that if a polypeptide/compound complex is detected, a compound that binds to a polypeptide of Claim 8 is identified. 16. A method for identifying a compound that binds to a polypeptide of Claim 8, comprising: a) contacting a compound with a polypeptide of Claim 8, in a cell, for a time sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a reporter gene sequence in the cell; and b) detecting the complex by detecting reporter gene sequence expression, so that if a polypeptide/compound complex is detected, a compound that binds to a polypeptide of Claim 8 is identified. 17. A method of producing the polypeptide of claim 8, comprising, a) culturing the host cell of claim 7 for a period of time sufficient to express the polypeptide contained within said cell; and b) isolating the peptide from the cell of step 1. 18. A polypeptide according to claim 8 capable of binding to the Interleukin-1 Receptor. 19. A polypeptide according to claim 8 which is an antagonist ofthe Interleukin-1 Receptor. 20. A method of modulating the biological activity of an Interleukin- 1 Receptor comprising contacting the receptor with the polypeptide of claim 8. 21. A polypeptide according to claim 8 wherein said polypeptide is labeled with a radioactive label. 22. The polypeptide of claim 8 wherein said polypeptide is coupled to a colorimetric label. 23. A method of labeling an Interleukin -1 receptor comprising contacting a labeled polypeptide of claim 21 with said receptor. 24. The method of claim 23, wherein said method is carried out in vitro. 25. The method of claim 24, wherein said method is carried out in vivo. 26. A kit comprising the polypeptide of claim 8. 27. An isolated polynucleotide encoding a polypeptide fragment ofthe amino acid sequence of SEQ DD NO: 5, wherein said fragment has a molecular mass as determined by SDS-PAGE of about 16 kDa or less. 28. The isolated polynucleotide of claim 27 wherein the molecular mass of said polypeptide fragment is about 15.5 kDa. 29. An isolated polypeptide fragment ofthe amino acid sequence of SEQ DD NO: 5, said polypeptide fragment having a molecular mass as determined by SDS- PAGE of about 16 kDa or less. 30. The isolated polypeptide of claim 29 wherein the molecular mass of said polypeptide fragment is about 15.5 kDa. 31. A fusion protein comprising the polypeptide fragment of claim 28 or 29 fused to a heterologous polypeptide. 32. A polynucleotide encoding the fusion protein of claim 31. 33. A collection of polynucleotides, the collection comprising the sequence information of at least one of SEQ DD NOS: 1 , 2, 4, 6 or 7 or a fragment thereof. 34. The collection of claim 33, wherein the collection is provided on a nucleic acid aπay. 35. The collection of claim 33, wherein the collection is provided in a computer-readable format. 36. A method of treatment for cancer involving elevated levels of IL-1 comprising the step of: administering to a patient in need thereof an amount of IL-1 Hyl effective to ameliorate symptoms of said cancer. 37. The method of claim 36 wherein the cancer is selected from the group consisting of breast adenocarcinoma, brain tumors, melanoma, myeloma, giant cell tumors of bone, acute myelogenous leukemia, oral epidermoid carcinoma and squamous cell carcinoma. 38. A method of treatment for inflammation comprising the step of: administering to a patient in need thereof an amount of EL-1 Hyl effective to ameliorate symptoms of said inflammation. 39. The method of claim 38 wherein the inflammation results from infection. 40. The method of claim 38 wherein the inflammation results from allergic reaction. 41. The method of claim 38 wherein the inflammation is associated with chronic bronchitis. 42. The method of claim 38 wherein the inflammation is associated with arthritis. 43. The method of claim 38 wherein the inflammation is associated with diabetes. 44. The method of claim 38 wherein the inflammation is associated with endotoxemia. 45. A method of treating an inflammatory disease state mediated by IL-18 comprising administering to a subject in need thereof an amount of IL-1 Hyl according to claim 8, or an active variant thereof, effective to inhibit IL-18 activity.

Inventors: FORD JOHN, PACE ANN, FORD, JOHN, PACE, ANN
Applicants: FORD JOHN, HYSEQ INC, PACE ANN, FORD, JOHN, HYSEQ, INC., PACE, ANN
Application year: 2000
Main classification: C12N15
IPC codes: A61K38, A61K49, A61K51, A61P1, A61P3, A61P11, A61P15, A61P19, A61P29, A61P31, A61P35, A61P37, A61P39, C07K14, C07K16, C12N1, C12N5, C12N15, C12P21, C12Q1, C12R1, G01N33, G01N37