Title

The role of interleukin-1 in the pathogenesis of rheumatoid arthritis

UMMS Affiliation

Department of Medicine, Division of Rheumatology

Date

6-1-2004

Document Type

Article

Medical Subject Headings

Animals; Arthritis, Rheumatoid; Humans; Interleukin-1; Macrophages; Models, Animal; Rabbits; Receptors, Interleukin-1; Tumor Necrosis Factor-alpha

Disciplines

Musculoskeletal Diseases | Rheumatology | Skin and Connective Tissue Diseases

Abstract

A significant body of experimental evidence has implicated the proinflammatory cytokine IL-1 in the pathogenesis of RA. For example, IL-1beta 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.

Rights and Permissions

Citation: Rheumatology (Oxford). 2004 Jun;43 Suppl 3:iii2-iii9. Link to article on publisher's site

Comments

At the time of publication, Jonathan Kay was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

15150426