Norihiro Nishimoto1. 1. Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan. norihiro@fbs.osaka-u.ac.jp
Abstract
PURPOSE OF REVIEW: Recent progress in cytokine studies has clarified the pathological roles played by cytokines and provided key evidence that antagonizing their actions can be therapeutic. The pathogenesis of rheumatoid arthritis, an autoimmune inflammatory disease, involves inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-1 and interleukin-6. Anti-tumour necrosis factor-alpha and anti-interleukin-1 therapies have been used successfully to treat rheumatoid arthritis, but they are not consistently effective. We therefore need further therapies for this refractory disease. Interleukin-6 is another target molecule for blockade in the treatment of rheumatoid arthritis. Tocilizumab is a humanized antihuman interleukin-6 receptor monoclonal antibody designed to block the actions of interleukin-6. This review addresses the pathological significance of interleukin-6 and the current status of anti-interleukin-6 therapy for rheumatoid arthritis. RECENT FINDINGS: The safety and efficacy of tocilizumab have been demonstrated in clinical trials conducted in patients with rheumatoid arthritis and other autoimmune inflammatory diseases, such as juvenile idiopathic arthritis and Crohn's disease. SUMMARY: Clinical studies have demonstrated the pathological significance of interleukin-6 and the safety and efficacy of anti-interleukin-6 therapy with tocilizumab. Blockade of interleukin-6 - the second generation of anticytokine therapy - may be a promising treatment for rheumatoid arthritis.
PURPOSE OF REVIEW: Recent progress in cytokine studies has clarified the pathological roles played by cytokines and provided key evidence that antagonizing their actions can be therapeutic. The pathogenesis of rheumatoid arthritis, an autoimmune inflammatory disease, involves inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-1 and interleukin-6. Anti-tumour necrosis factor-alpha and anti-interleukin-1 therapies have been used successfully to treat rheumatoid arthritis, but they are not consistently effective. We therefore need further therapies for this refractory disease. Interleukin-6 is another target molecule for blockade in the treatment of rheumatoid arthritis. Tocilizumab is a humanized antihuman interleukin-6 receptor monoclonal antibody designed to block the actions of interleukin-6. This review addresses the pathological significance of interleukin-6 and the current status of anti-interleukin-6 therapy for rheumatoid arthritis. RECENT FINDINGS: The safety and efficacy of tocilizumab have been demonstrated in clinical trials conducted in patients with rheumatoid arthritis and other autoimmune inflammatory diseases, such as juvenile idiopathic arthritis and Crohn's disease. SUMMARY: Clinical studies have demonstrated the pathological significance of interleukin-6 and the safety and efficacy of anti-interleukin-6 therapy with tocilizumab. Blockade of interleukin-6 - the second generation of anticytokine therapy - may be a promising treatment for rheumatoid arthritis.
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