IRAK contributes to burn-triggered myocardial contractile dysfunction.

Abstract

Major burn injury causes myocardial contractile dysfunction, but the molecular basis of this physiological response is incompletely understood. Previous studies demonstrated a role for the interleukin-1 receptor-associated kinase (IRAK) in the cardiac response to acute lipopolysaccharide administration as well as congestive heart failure. In this study, we examined the contribution of IRAK to burn-mediated cardiac responses. After burn injury, hearts from wild-type and IRAK-deficient mice were compared for intracellular signaling pathway activation and contractile function. IRAK-deficient hearts showed impaired activation of kinases that function downstream of IRAK and were partially protected against burn-induced contractile dysfunction. The findings demonstrate that IRAK and the Toll/interleukin-1 pathways participate in the response to large body surface area burns that leads to impaired cardiac contractility.