title: Targeting gp130 to prevent inflammation and promote insulin action.
abstract: 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.
authors.affiliation: Cellular & Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kraakman
authors.forename: T L
authors.initials: TL
authors.lastname: Allen
authors.forename: M
authors.initials: M
authors.lastname: Whitham
authors.forename: P
authors.initials: P
authors.lastname: Iliades
authors.forename: H L
authors.initials: HL
authors.lastname: Kammoun
authors.forename: E
authors.initials: E
authors.lastname: Estevez
authors.forename: G I
authors.initials: GI
authors.lastname: Lancaster
authors.forename: M A
authors.initials: MA
authors.lastname: Febbraio
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D050822:Cytokine Receptor gp130 / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007328:Insulin; D015850:Interleukin-6; D050822:Cytokine Receptor gp130; C502936:tocilizumab
keywords: IL-6 signalling; cytokines; insulin resistance; obesity