Effects of Intranasal Administration of Recombinant Murine Interferon-γ on Murine Acute Myocarditis Caused by Encephalomyocarditis Virus

Abstract
Background —Viral myocarditis has been strongly implicated in the pathogenesis of dilated cardiomyopathy as well as acute myocarditis. Among the antiviral therapies, interferons (IFNs) have been widely studied and become very important in clinical practice. Methods and Results —To investigate the possibilities of IFN therapy in viral myocarditis, we analyzed the effects of recombinant murine interferon (mIFN)-γ and natural mIFN-α/β by the intranasal and intramuscular routes on the development of acute murine myocarditis caused by encephalomyocarditis virus. Both mIFN-γ and mIFN-α/β treatment by either route significantly increased the survival rate; none of the mIFN-γ–treated mice died. The effect of mIFN-γ was significantly greater than that of mIFN-α/β. Furthermore, intranasal administration of mIFN-γ significantly suppressed virus replication and inflammation in the heart. Conclusions —Our data demonstrate that IFN therapy, especially intranasal administration of IFN-γ, dramatically improved the prognosis of acute murine viral myocarditis by suppressing virus replication and raises the possibility of antiviral therapy with IFN-γ in patients with acute myocarditis.