The pathogenesis of postinfectious myocarditis.
Myocarditis is an important cause of heart failure among adolescents and young adults. A remarkable observation is the discrepancy between the limited overt evidence of myocyte injury and the global impairment of left ventricular function. This discrepancy has stimulated suggestions that immunological mechanisms contribute to cardiac damage. We have developed two murine models of myocarditis, one elicited by cardiotropic Coxsackie B3 (CB3) virus infection and the other by cardiac myosin immunization, to better analyze the pathogenetic mechanisms responsible for immune-mediated heart-muscle disease. Both virus infection and myosin immunization produce myocardial inflammation and elicit heart-reactive antibodies which bind to the myocardium in vivo and which recognize the cardiac myosin heavy chain. Each model offers unique advantages. The virus-induced disease more closely resembles human myocarditis; myosin immunization isolates the autoimmune components of the disease since no virus infection is involved. We have also distinguished strains of mice resistant to autoimmune myocarditis (such as B10.A) from those susceptible to the autoimmune phase of disease (such as A.CA and A/J). Mice from a resistant strain to virus-or myosin-induced autoimmune heart disease develop myocardial inflammation and myosin antibodies if co-treated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 when infected or immunized. Thus, cytokines can modulate the outcome of cardiotropic virus infection and enhance its autoimmune sequela. We also found that blocking IL-1 receptor inhibits autoimmune myocarditis in genetically susceptible mice.
Rose
N R
NR
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Hill
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000821:virology*; D003384:Coxsackievirus Infections; D004195:Disease Models, Animal; D029822:Enterovirus B, Human; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000209:etiology* / Q000821:virology*; D009218:Myosins / Q000633:toxicity
D009218:Myosins