IL-1 inhibitors: novel agents in the treatment of rheumatoid arthritis

IL-1 is a pleiotropic cytokine shown to play a major role in synovitis and in the mechanisms that lead to the progressive joint destruction of rheumatoid arthritis (RA). IL-1 receptor antagonist (IL-1Ra), a member of the IL-1 family, binds IL-1 receptors but does not induce a cellular response. IL-1Ra competitively inhibits the binding of IL-1 to its cell surface receptors and thus acts as an endogenous anti-inflammatory mediator. In different experimental animal models of arthritis systemic administration of IL-1Ra, or local delivery into the joints by gene therapy attenuated the severity of the inflammatory response and reduced articular destruction. In addition, treatment of RA patients with IL-1Ra led to an improvement in different clinical and biological parameters and to a reduction in the radiological signs of joint erosions. Recently, interesting results were obtained using IL-1Ra in combination with methotrexate, a well-known antirheumatic drug, or in combination with other strategies designed to block the effects of tumour necrosis factor (TNF)-alpha. Encouraging results also have been reported in both in vitro and in vivo experimental models of arthritis by using other strategies designed to block the effects of IL-1.