IFN-beta in rheumatoid arthritis.
IFN-beta is a cytokine with pleiotropic effects and is expressed in rheumatoid synovial tissue. Based on in vitro work and experiments in animal models of rheumatoid arthritis (RA), the effects are mainly anti-inflammatory. Of special interest is the ability of IFN-beta to reduce the secretion of TNF-alpha, IL-1 beta, and IL-6, which are all key players in the pathogenesis of RA. At the same time IFN-beta could enhance the production of anti-inflammatory mediators like IL-1 receptor antagonist (IL-1Ra) and IL-10. Treatment of mice and monkeys with collagen-induced arthritis with daily IFN-beta injections resulted in clinical improvement, decreased synovial inflammation, and protection against joint destruction. Similar data were obtained after IFN-beta gene therapy. However, treatment of RA patients with IFN-beta has been unsuccessful so far, presumably due to pharmacokinetic issues. Novel approaches leading to constitutive IFN-beta production at the site of inflammation may be required to induce clinical efficacy in patients.
Tak
Paul Peter
PP
Division of Clinical Immunology and Rheumatology Academic Medical Center/ University of Amsterdam, The Netherlands. P.P.Tak@amc.uva.nl
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D000882:Haplorhini; D006801:Humans; D007249:Inflammation; D016899:Interferon-beta / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use*; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D012795:Sialoglycoproteins / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D016753:Interleukin-10; D016899:Interferon-beta