title: Lessons learned from experimental myocarditis.
abstract: We have developed murine models of viral myocarditis induced by encephalomyocarditis (EMC) virus in which severe myocarditis, congestive heart failure and dilated cardiomyopathy occur in high incidence. From these models, we have learned the natural history and pathogenesis and assessed not only new diagnostic methods but also therapeutic and preventive interventions. Autoantibodies against cardiac troponin I appeared in spontaneously developing autoimmune myocarditis in PD-1 deficient mice, who lack the T-cell receptor costimulatory molecule PD-1. The passive transfer of this antibody induced myocardial dysfunction. Later, this autoantibody was found in patients with myocarditis. Mast cell deficiency had beneficial effects in the viral myocarditis model, and anti-allergic agents prevented viral myocarditis. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blocker and an aldosterone receptor antagonist improved viral myocarditis, suggesting that the renin-angiotension-aldosterone system may play an important role in the pathogenesis of viral myocarditis. Differential modulation of cytokine production was seen with various calcium channel blockers, and some calcium channel blocker improved viral myocarditis. Viral infection could lead to increased synthesis of immunoglobulin light chains (FLC). Serum levels of FLC were increased in myocarditis, and exogenously given FLC inhibited viral replication and improved myocarditis. We suggest that a strategy of drug development specifically addressing inflammation in myocarditis may provide increased benefit in terms of target organ damage.
authors.affiliation: Department of Cardiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, 160-8402, Tokyo, Japan. amatsumori@clock.ocn.ne.jp
authors.forename: A
authors.initials: A
authors.lastname: Matsumori
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines