The heat is off: immunosuppression for myocarditis revisited

Abstract

Non-ischaemic, dilated cardiomyopathy (DCM) is an important cause of heart failure and heart transplantation, with a prevalence of 36.5 per 100 000 in the USA.1 Depending on the histological or immunohistological criteria employed, myocarditis is present in ∼10–50% of heart biopsy samples taken from patients with acute non-ischaemic DCM.2 When T cell and macrophage number are quantified by immunohistological methods or the definition of myocarditis is broadened to include expression of class II major histocompatability complex antigens and adhesion molecules, myocarditis is present in 40–50% of patients with chronic DCM.3 Of the many known causes of myocarditis, viral infection is perhaps the most important. From 25 to 40% of myocardial samples from patients with chronic, unexplained DCM contain viral genomes.4 Although a host of viruses have been implicated in myocarditis and DCM, viral infection is not always accompanied by inflammation. Experimental studies in inbred rodents suggest a model of pathogenesis of viral and post-viral myocarditis that helps to explain these clinical observations ( Figure 1 ).5 Viruses cause initial myocyte damage and elicit a robust innate immune response that includes Toll-like receptor activation, cytokines, nitric oxide expression, and the recruitment of natural killer T cells. In the days following an initial injury, antigen-specific T cells and antibodies develop as the immune reaction adapts to the specific pathogen. In many cases, the viral infection is cleared and the immune reaction downregulates with little or no lasting cardiac damage. In a minority of cases, either the virus or the inflammatory reaction persists and contributes to cardiomyopathy. However, a replication-deficient enterovirus may cause cardiomyopathy by cleavage of host cytoskeletal proteins without eliciting an immune response.6 Through molecular mimicry, a chronic immune reaction may be stimulated by host antigens such as cardiac myosin or laminin, which resemble pathogen proteins, … *Corresponding author. Tel: +1 507 284 3680, Fax: +507 266 0228, Email: cooper.leslie{at}mayo.edu