Vol. 299, Issue 2, 645-651, November 2001

Immunoglobulin Treatment Prevents Congestive Heart Failure in Murine Encephalomyocarditis Viral Myocarditis Associated with Reduction of Inflammatory Cytokines

Chiharu Kishimoto¹, Hitoshi Takada, Hiroshi Kawamata, Miho Umatake and Hiroshi Ochiai

The Second Department of Internal Medicine (H.T.), Departments of Oriental Medicine (H.K.) and Human Science (M.U., H.O.), Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan

We have previously shown that immunoglobulin therapy suppressed murine coxsackievirus B3 myocarditis. In the present study, we examined the effects of immunoglobulin upon murine myocarditis induced by encephalomyocarditis virus, which is not pathogenic to humans. Antiviral activity of immunoglobulin (Venilon) against encephalomyocarditis virus could not be detected in vitro. The production of cytokines was decreased in virus-infected macrophages by the treatment of immunoglobulin in vitro. Immunoglobulin (1 g/kg/day) was administered intraperitoneally to the virus-infected C₃H/He mice daily for 2 weeks, beginning simultaneously with virus inoculation in experiment I and on day 14 after virus inoculation in experiment II. In experiment I, survival rate did not differ significantly between immunoglobulin-treated and untreated groups. In experiment II, survival rate was higher in immunoglobulin compared with control groups. Immunoglobulin administration suppressed the development of myocardial necrosis with T-lymphocyte infiltrates in mice not only in the acute viremic but in the chronic aviremic stages concomitantly associated with the reduction of inflammatory cytokines, i.e., tumor necrosis factor-, interferon-, macrophage inflammatory protein-2, and interleukin-6. Taken together, immunoglobulin therapy could have the potential to prevent congestive heart failure.