Immunoglobulin treatment ameliorates murine myocarditis associated with reduction of neurohumoral activity and improvement of extracellular matrix change

OBJECTIVES We examined effects of immunoglobulin on murine myocarditis indu ced by encephalomyocarditis virus, not pathogenic to humans, and analyzed t he plasma cytokine and catecholamine levels and the changes of the extracel lular matrix with or without the treatment. BACKGROUND We have previously shown that immunoglobulin therapy suppressed murine coxsackievirus B3 myocarditis by an antiviral effect. However, it is not yet determined whether beneficial effects of immunoglobulin for myocar ditis are due to antiviral effects or to other unknown effects. METHODS Antiviral activity of human immunoglobulin (Polyglobin-N) against e ncephalomyocarditis virus was determined in vitro. Immunoglobulin (1 g/kg/d ay) was administered intraperitoneally to the virus-infected mice daily for two weeks, beginning simultaneously with virus inoculation in experiment I and on day 14 after virus inoculation in experiment II. RESULTS Antiviral activity of immunoglobulin could not be detected in the a ssay of a plaque-reduction method in vitro. The in vivo study showed that i mmunoglobulin administration ameliorated both myocardial necrosis with inte rstitial fibrin deposition in experiment I and interstitial fibrosis with t he improvement of ventricular remodeling in experiment II by the reduction of plasma catecholamines, interferon-alpha, and soluble intercellular adhes ion molecule-1. CONCLUSIONS Immunoglobulin therapy could suppress myocarditis associated wi th the improvement of extracellular matrix changes by the reduction of neur ohumoral activity. (C) 2000 by the American College of Cardiology.