Patent ID: 6936586

Claim:
A polypeptide in at least partially purified form, which is six to 20 amino acids in length, and which comprises the following sequence X A -X 4 -X B -X 5 -X C -X 6 wherein X 4 and X 5 are independently selected from the group consisting of Met, Ile, Leu, Val, norvaline, norleucine, methionine-S-oxide, N-methylvaline, N-methyl isoleucine, allo-leucine, and their D-isomers; X 6 is selected from the group consisting of Asn, Asp, Gln, Glu, and their D-isomers, X A is L-Thr or D-Thr, X B is L-Lys, L-Orn, L-Dab, or one of their D-isomers, and X C is L-Arg or D-Arg, wherein at least one of the following conditions (I)—(IV) is true: I) at least one of X A , X B , X C , X 4 , X 5 or X 6 is an amino acid other than a genetically encoded amino acid, the genetically encoded amino acids being here defined as amino acids selected from the group consisting of glycine, L-alanine, L-serine, L-threonine, L-leucine, L-isoleucine, L-methionine, L-valine, L-cysteine, L-asparagine, L-aspartic acid, L-glutamine, L-glutamic acid, L-arginine, L-lysine, L-histidine, L-phenylalanine, L-tryptophan, L-tyrosine, and L-proline, II) the polypeptide is cyclized, III) the aminoterminal amino acid residue is acylated, or IV) the carboxyterminal amino acid residue is amidated, said polypeptide having at least one of the following properties: a) induces inhibition of spontaneous IL-S production by human monocytes, b) induces inhibition of IL-1β induced IL-8 production by human peripheral blood mononuclear cells (PEMC), c) induces production of interleukin- 1 receptor antagonistic protein (IRAP) by human monocytes, d) induces chemotactic migration of CD8+ human T lymphocytes in vitro, e) desensitizes human CD8+ T cells resulting in an unresponsiveness towards rhIL-10, f) suppresses the chemotactic response of CD4+ T human lymphocytes towards IL-8, g) suppresses the chemotactic response of human monocytes towards MCAF/MCP-1, h) inhibits class II MHC molecule expression on human monocytes stimulated by IFN-γ, i) induces the production of IL-4 by cultured normal human CD4+ T cells, j) reduces TNFα production in human mixed leukocyte reaction, or k) downregulates TNFα and IL-8 production in a rabbit model of bile acid induced acute pancreatitis and reduces neutrophil infiltration in the lungs of the treated rabbits.