Targeting gp130 to prevent inflammation and promote insulin action

Obesity and type 2 diabetes are now the most prevalent metabolic diseases in the Western world and the development of new strategies to treat these metabolic diseases is most warranted. Obesity results in a state of chronic low‐grade inflammation in metabolically active tissues such as the liver, adipose tissue, brain and skeletal muscle. Work in our laboratory has focussed on the role of the cytokine interleukin‐6 (IL)‐6 and other IL‐6‐like cytokines that signal through the gp130 receptor complex. We have focussed on the role of blocking IL‐6 trans‐signalling to prevent inflammation on the one hand, and activating membrane‐bound signalling to promote insulin sensitivity on the other hand. Since the cloning of the IL‐6 gene nearly 30 years ago, a pattern has emerged associating IL‐6 with a number of diseases associated with inflammation including rheumatoid arthritis (RA), Crohn's disease and several cancers. Accordingly, tocilizumab, an IL‐6 receptor‐inhibiting monoclonal antibody, is now useful for the treatment of RA. However, this may not be the most optimal strategy to block inflammation associated with IL‐6 and may result in unwanted side effects that, paradoxically, could actually promote metabolic disease.