title: Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype.
abstract: Hyperglycemia in critical illness is a common complication and a strong independent risk factor for morbidity and death. Intensive insulin therapy decreases this risk by up to 50%. It is unclear to what extent this benefit is due to reversal of glucotoxicity or to a direct effect of insulin, because antiinflammatory effects of insulin have already been described, but the underlying mechanisms are still poorly understood. The insulin receptor is expressed on resting neutrophils, monocytes, and B cells, but is not detectable on T cells. However, significant up-regulation of insulin receptor expression is observed on activated T cells, which suggests an important role during T cell activation. Exogenous insulin in vitro induced a shift in T cell differentiation toward a T helper type 2 (Th2)-type response, decreasing the T helper type 1 to Th2 ratio by 36%. This result correlated with a corresponding change in cytokine secretion, with the interferon-gamma to IL-4 ratio being decreased by 33%. These changes were associated with increased Th2-promoting ERK phosphorylation in the presence of insulin. Thus, we demonstrate for the first time that insulin treatment influences T cell differentiation promoting a shift toward a Th2-type response. This effect of insulin in changing T cell polarization may contribute to its antiinflammatory role not only in sepsis, but also in chronic inflammation associated with obesity and type 2 diabetes.
authors.affiliation: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney-Darlinghurst, New South Wales 2010, Australia. a.viardot@garvan.org.au
authors.forename: Alexander
authors.initials: A
authors.lastname: Viardot
authors.forename: Shane T
authors.initials: ST
authors.lastname: Grey
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Donald
authors.initials: D
authors.lastname: Chisholm
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D007328:Insulin; D015847:Interleukin-4; D007371:Interferon-gamma; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases