Role of interleukin‐33 in sepsis‐induced myocardial dysfunction

Abstract

The disruption of myocardial extracellular matrix (ECM) protein has been implicated in myocardial dysfunction during sepsis. However, the underlying mechanism(s) are not clear. Interleukin‐ 33 (IL‐33) is a cytokine which can regulate collagen synthesis in various cardiac pathologies. The purpose of the present study is to test whether IL‐33 contributes to the sepsis‐induced myocardial dysfunction through regulation of matrix metalloprotease‐9 (MMP‐ 9).MethodsIn vivo, feces‐induced peritonitis (FIP) in mice and in vitro LPS treatments to isolated cardiomyocytes were used in the study.ResultsIn mice with FIP, myocardial IL‐33 and MMP‐9 expression were increased and myocardial contractility was decreased. Myocardial function in mice with FIP was improved when the mice were treated with soluble ST2 (sST2), a decoy receptor of IL‐33. The in vitro, expression of IL‐33 and MMP‐9 in cardiomyocytes treated with LPS was increased. Addition of sST2 prevented the increase in MMP‐9 expression in LPS treated myocytes.ConclusionOur results indicate IL‐33 plays an important role in mediating sepsis‐induced myocardial dysfunction by regulation of myocyte MMP‐9 expression. (Supported by the Department of National Defense, Canadian Forces Medical Group)