Rheumatoid Arthritis: Anticytokine Therapies on the Horizon
Authors: William J. Koopman
Journal: Annals of Internal Medicine (1998)

Editorials1 February 1998Rheumatoid Arthritis: Anticytokine Therapies on the HorizonWilliam J. Koopman, MD and Larry W. Moreland, MDWilliam J. Koopman, MDThe University of Alabama at Birmingham; Birmingham, AL 35294Search for more papers by this author and Larry W. Moreland, MDThe University of Alabama at Birmingham; Birmingham, AL 35294Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-3-199802010-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The agents currently used to treat aggressive rheumatoid arthritis, the so-called disease-modifying antirheumatic drugs, were generally not developed for that purpose. At best, they reduce the destructive component of the disease modestly and inconsistently.Although the cause of rheumatoid arthritis remains unknown, recent advances in molecular technology have facilitated the identification of distinct cell subsets, cell surface markers, and cell products that contribute to the inflammatory and destructive components of the disease. This enhanced understanding affords new opportunities to direct specific therapies at relevant disease molecules and cells. In particular, increasing evidence implicates interleukin-1 and tumor necrosis factor-α (TNF-α) as ...References1. Arend WP, Dayer JM. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor α in rheumatoid arthritis. Arthritis Rheum. 1995; 38:151-60. Google Scholar2. Wooley PH, Whalen JD, Chapman DL, Berger AE, Richard KA, Aspar DG, et al. 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A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor α for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med. 1997; 337:1029-35. Google Scholar16. Tartaglia LA, Weber RF, Figari IS, Reynolds C, Palladino MA Jr, Goeddel DV. The two different receptors for tumor necrosis factor mediate distinct cellular responses. Proc Natl Acad Sci U S A. 1991; 88:9292-6. Google Scholar17. Moreland LW, Margolies G, Heck LW Jr, Saway A, Blosch C, Hanna R, et al. Recombinant soluble tumor necrosis factor receptor (p80) fusion protein: toxicity and dose finding trial in refractory rheumatoid arthritis. J Rheumatol. 1996; 23:1845-8. Google Scholar18. Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med. 1997; 337:141-7. Google Scholar19. Ralph P, Nakoinz I, Sampson-Johannes A, Fong S, Lowe D, Min HY, et al. IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol. 1992; 148:808-14. Google Scholar20. Vannier E, Miller LC, Dinarello CA. Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but upregulates gene expression and synthesis of interleukin 1 receptor antagonist. Proc Natl Acad Sci U S A. 1992; 89:4076-80. Google Scholar21. Trepicchio WL, Wang LL, Bozza M, Dorner AJ. Interleukin-11 regulates macrophage effector function through inhibition of NF-kB. J Immunol. [In press.] Google Scholar Author, Article, and Disclosure InformationAuthors: William J. Koopman, MD; Larry W. Moreland, MDAffiliations: The University of Alabama at Birmingham; Birmingham, AL 35294Grant Support: In part by National Institutes of Health grant R1AR44384A. Dr. Koopman is a principal investigator for studies sponsored by Sankyo, Inc., and has participated in clinical trials sponsored by Centocor, The Immune Response Corporation, and Immunex. Dr. Moreland is the Director of the Arthritis Clinical Intervention Program at The University of Alabama at Birmingham; has been a principal investigator for clinical trials sponsored by several pharmaceutical companies; and has been a consultant for Alexion Pharmaceuticals, Amgen, Biomatrix, Boehringer Ingelheim, Centocor, Connectics, Glaxo-Wellcome, Immunex, Knoll-BASF, Pharmacia/Upjohn, Schering-Plough Research Institute, Searle, SmithKline Beecham, TAP Holdings, and Wyeth.Corresponding Author: William J. Koopman, MD, Department of Medicine, The University of Alabama at Birmingham, 402 Diabetes Education and Research Building, 1808 Seventh Avenue South, Birmingham, AL 35294-0012. 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