Eosinophils are required for the development of myosin-induced myocarditis and dilated cardiomyopathy (135.28)

Abstract

Abstract Eosinophilic infiltration has been associated with severe myocarditis and depressed cardiac function; however, demonstrating a causal relationship between eosinophils and myocarditis and dilated cardiomyopathy (DCM) has long remained elusive. We show here that Interleukin-5 (IL-5) is dispensable for the recruitment of eosinophils into the inflamed heart, the development of myosin-induced myocarditis (EAM) and the progression of EAM to DCM. However, IL-5-overexpressing transgenic mice developed peripheral eosinophilia, severe eosinophilic myocarditis, increased myocardial fibrosis and accelerated progression to DCM. In addition, eosinophil-deficient (dblGATA1) mice developed attenuated EAM, decreased myocardial fibrosis and greatly improved left ventricular function. Treatment with resorcinol, a specific inhibitor of eosinophilic peroxidase, significantly decreased myocarditis and myosin-induced heart hypertrophy. We conclude that eosinophils are required for the development of EAM, and the progression to DCM, at least in part through their secretion of eosinophilic peroxidase.