Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 9, Issue -, Pages 3242-3247Publisher
IMR PRESS
DOI: 10.2741/1475
Keywords
rheumatoid arthritis; IFN-beta; synovial tissue; treatment; biologicals
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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.
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