Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage.

ABSTRACT

Destruction of articular joints occurs progressively in patients with rheumatoid arthritis (RA). Although the exact aetiology of RA has not been fully elucidated, a large body of evidence supports a role for interleukin-1 (IL-1) in cartilage and bone erosion. In vitro studies suggest that IL-1 can cause cartilage destruction by stimulating the release of matrix metalloproteinases and other degradative products, and it can increase bone resorption by stimulating osteoclast differentiation and activation. In animal models of RA, blocking the effects of IL-1 with either IL-1 receptor antagonist (IL-1Ra; endogenous), anti-IL-1 monoclonal antibodies, or soluble IL-1 type II receptors significantly reduced cartilage destruction and bone erosion. Gene therapy with IL-1Ra was also effective in reducing joint destruction in experimental RA and osteoarthritis (OA) models. In clinical studies, anakinra, a human recombinant IL-1 receptor antagonist (IL-1ra; exogenous), significantly slowed radiographic progression of RA relative to placebo and significantly reduced clinical symptoms when used as monotherapy or in addition to existing methotrexate therapy. These results demonstrate that blocking IL-1 protects bone and cartilage from progressive destruction in RA.