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.
Gabay
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Division of Rheumatology, University Hospital of Geneva, 26 Avenue Beau-Sejour, 1211 Geneva 14, Switzerland. Cem.Gabay@hcuge.ch.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational; D015316:Genetic Therapy; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D023421:Models, Animal; D012795:Sialoglycoproteins / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D015507:Drugs, Investigational; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins