Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice

Four week old C3H-mice were infected with CBV3 and received twice daily, for 7 consecutive days (from one day before to 5 days post-virus inoculation) treatment with MMF via oral gavage. Treatment with MMF resulted in a significant reduction in the development of CBV-induced myocarditis as assessed by morphometric analysis, i.e. 78% reduction when MMF was administered at 300 mg/kg/day (p < 0.001), 65% reduction at 200 mg/kg/day (p < 0.001), and 52% reduction at 100 mg/kg/day (p = 0.001). The beneficial effect could not be ascribed to inhibition of viral replication since titers of infectious virus and viral RNA in heart tissue were increased in MMF-treated animals as compared to untreated animals.The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model.Viral myocarditis is a common pathological condition detected in approximately 1% of unselected asymptomatic individuals [1]. Many viruses have been shown to be involved as causative agents, but the principal agents belong to enteroviruses in general and coxsackieviruses in particular [2,3]. The proportion of cases of myocarditis with coxsackieviral ethiology varies but can in 25–50% of the cases be attributed to coxsackie B group viruses (CBV) [4,5]. Although most enterovirus-related cardiac illnesses are subclinical, severe arrythmias and sudden cardiac death may appear. About 10 to 20% of symptomatic patients will eventually develop chronic cardiac disease, which may progress to dilated cardiomyopathy, a severe pathological condition, often requiring heart transplantation [6-8]. Overall, the enteroviral genome is present in the hearts of 15–20% of patients with dilated cardiomyopathy [4,5,9,10]. Both direct viral injury and the immune response of the host are believed to play a role in the pathogenesis of viral heart disease [11]. Recent studies in mouse models show that direct viral-induced damage to the heart is necessary to cause CBV3-induced myocarditis [12