Interleukin-6; pathogenesis and treatment of autoimmune inflammatory diseases

Abstract

Interleukin-6 (IL-6), originally identified as a B cell stimulatory factor-2, is a typical cytokine featuring redundancy and pleiotropic activity. A transient expression of IL-6 participates in host defense against acute environmental stress such as infections and injuries by activating immune responses, hematopoiesis and acute phase reactions. However, its abnormal, persistent production plays an important pathological role in the development of various autoimmune inflammatory diseases, so that it was hypothesized that IL-6 blockade would constitute a novel strategy for the treatment of such diseases and to this purpose tocilizumab, a humanized antiIL-6 receptor monoclonal antibody, was developed. Clinical trials have indeed proved the efficacy and tolerable safety of tocilizumab for patients with moderate to severe rheumatoid arthritis, and it is now used as a“ “ “ “made-in-Japan”innovative biologic for rheumatoid arthritis in more than 90 countries worldwide, as well as for patients with Castleman's disease and systemic and polyarticular juvenile idiopathic arthritis. Moreover, favorable results of recent clinical trials or case reports of off-label use with tocilizumab indicate that it is likely to be broadly applicable for the treatment of various autoimmune inflammatory diseases. Its wider application for various diseases as well as clarification of the mechanism(s) through which IL-6 blockade becomes clinically efficacious and of the etiology of dysregulated persistent IL-6 production in such diseases are important issues for future studies.