The Biological Effects of Interleukin-6 and Their Clinical Applications in Autoimmune Diseases and Cancers

Interleukin-6 (IL-6) is one of the pro-infl ammatory cytokines involved in pathogenesis of various autoimmune and chronic infl ammatory diseases. IL-6 through binding to its cellular receptor can transduce both classical- and trans-signaling pathways. Overproduction of circulating IL-6 can be detected in patients with different autoimmune diseases. Tocilizumab, a humanized monoclonal antibody against IL-6 receptor, can block IL-6-mediated signaling and has been approved for the treatment of rheumatoid arthritis and Castleman's disease. Besides, expression of IL-6 may promote tumorigenesis and has been detected in various tumors, including multiple myeloma, colorectal cancer, breast cancer, lymphoma, breast cancer and lung cancer. Furthermore, increased levels of circulating IL-6 are associated with poor prognosis and cachexia in cancer patients. Monotherapy with IL-6 blockade or a combination therapy with both IL-6 blockade and conventional chemotherapy may reduce the progression of cancer and improve the status of cachexia in cancer patients. Finally, based upon the known biological effects of IL-6, diseases, other than autoimmune diseases and cancers, potentially to be anti-IL-6 candidates will be briefl y discussed.