Therapeutic effects of interleukin‐6 blockade in a murine model of polymyositis that does not require interleukin‐17A

Objective To explore new molecular targets in the treatment of polymyositis (PM) by examining a recently established murine model of PM, C protein–induced myositis (CIM), for involvement of an interleukin‐6 (IL‐6)/IL‐17A pathway. Methods CIM was induced by immunizing wild‐type mice as well as IL‐6–null and IL‐17A–null C57BL/6 mice with recombinant mouse skeletal C protein fragments. Some mice were treated with anti–IL‐6 receptor (anti–IL‐6R) monoclonal antibodies or control antibodies. Muscle tissue samples were examined histologically and immunohistochemically. Results The syngeneic C protein fragments successfully induced inflammation in the skeletal muscles of wild‐type mice. IL‐6 was expressed by mononuclear cells, especially in macrophages, infiltrating in the muscles. IL‐6–null mice developed myositis with significantly lower incidence and milder severity than wild‐type mice. In contrast, IL‐17A–null mice were as susceptible to CIM as wild‐type mice. Intraperitoneal administration of anti–IL‐6R monoclonal antibodies, but not of control monoclonal antibodies, ameliorated CIM both preventively and therapeutically. Conclusion Our findings indicate that IL‐6 is critically involved in the development of CIM. Although many other autoimmune models require IL‐6 for differentiation of pathogenic T cells producing IL‐17A, IL‐17A was dispensable in CIM. Nevertheless, treatment with anti–IL‐6R antibodies was effective. IL‐6 blockade is potentially a new approach to the treatment of autoimmune myositis, via processes distinct from interference in the IL‐6/IL‐17A pathway.