Rheumatology 2004; 43: III2-III9
Rheumatology Vol. 43 Suppl. 3 © British Society for Rheumatology 2004; all rights reserved
Supplement Article |
The role of interleukin-1 in the pathogenesis of rheumatoid arthritis
Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts, and 1Cleveland Clinic Foundation, Cleveland, Ohio, USA
Correspondence to: J. Kay, Rheumatology Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA (e-mail: jkay{at}partners.org) or L. Calabrese, Cleveland Clinic Foundation, Department of Rheumatology, 9500 Euclid Avenue, Cleveland, OH 44195, USA (e-mail: calabrl{at}ccf.org).
Abstract
A significant body of experimental evidence has implicated the proinflammatory cytokine IL-1 in the pathogenesis of RA. For example, IL-1ß overexpression in rabbit knee joints causes arthritis with clinical and histological features characteristic of RA, whereas IL-1 deficiency is associated with reduced joint damage. In experimental models, IL-1 blockers, including IL-1 receptor antagonist (IL-1Ra), significantly reduce clinical and histological disease parameters. In RA patients, plasma and synovial fluid concentrations of IL-1 are elevated, and these correlate with various parameters of disease activity. The production of endogenous IL-1Ra, however, appears to be insufficient to balance these higher IL-1 levels. The efficacy of blocking IL-1 in patients with active RA has been established in controlled clinical trials of anakinra, a recombinant human IL-1Ra (r-metHuIL-1ra). When used alone or in combination with methotrexate, anakinra significantly reduces the clinical signs and symptoms of RA compared with placebo. Taken together, these results indicate that IL-1 plays an important role in the pathogenesis of RA.
KEY WORDS: Anakinra, Biological therapy, Inflammation, Interleukin-1, Interleukin-1 receptor antagonist, Joint damage, Pathogenesis, Rheumatoid arthritis
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