Tocilizumab, a humanized anti‐interleukin‐6 receptor antibody, for the treatment of autoimmune disorders

Abstract

AbstractThe cytokine interleukin (IL)‐6 has a wide range of biological activities. It contributes to host defense against pathogens by inducing immune responses, hematopoiesis, and acute‐phase reactions. However, dysregulation of IL‐6 production plays a significant pathological role in various autoimmune and chronic inflammatory disorders. Because IL‐6 blockade was anticipated to provide a novel strategy for the treatment of such diseases, tocilizumab, a humanized anti‐IL‐6 receptor antibody, was developed. Clinical trials have demonstrated the efficacy of tocilizumab for patients with moderate to severe rheumatoid arthritis, resulting in approval in more than 90 countries worldwide of this innovative biologic for the treatment of rheumatoid arthritis. Tocilizumab was also approved in Japan for the treatment of Castleman's disease and juvenile idiopathic arthritis. Results of recent pilot or case studies have indicated that tocilizumab may become a novel drug for various other autoimmune disorders, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and vasculitis syndrome, as well as inflammatory disorders such as adult‐onset Still's disease, Crohn's disease, amyloid A amyloidosis, polymyalgia rheumatica, and spondylarthritides. It has been demonstrated that an imbalance of CD4‐positive T‐helper subsets [Th17 and/or Th1 >> regulatory T cells (Treg)] plays a major role in the development of several autoimmune disorders. In murine models of autoimmune disorders, the anti‐IL‐6 receptor antibody induced Treg and inhibited Th17 and/or Th1 differentiation, indicating that tocilizumab treatment may be able to repair this imbalance in human diseases as well. Drug Dev Res 72:717–732, 2011. © 2011 Wiley Periodicals, Inc.