Low-dose oral use of interferon inhibits virally induced myocarditis

Cytomegalovirus (CMV) infection has been associated with the development of myocarditis in humans. Our established mouse model for CMV myocarditis allows detailed investigation of the immunopathogenic mechanisms and therapies for cardiovascular disease. The type I interferons (IFN-alpha/beta) are part of the innate immune response to CMV infections. Previously, we have reported that daily treatment with low doses of murine IFN-alpha/beta administered by the oral-mucosal route significantly reduces early virus replication of murine CMV in the spleen and liver of infected mice. The oral-mucosal route provides an alternate delivery system to the current modes of IFN administration and is associated with fewer side effects. Since prophylactic treatment with type 1 IFNs may result in both antiviral and immunomodulatory effects that may lessen the development of disease, we wished to study the effect of IFN-alpha/beta on the development of myocarditis. Low-dose oral use of type I IFN (10 IU/day for 7 days prior to virus infection) did not abrogate myocarditis but suppressed the inflammatory response in both the acute and chronic phase of the disease. Furthermore, low-dose oral use of IFN was as effective at inhibiting myocarditis as a single injection of a high dose of IFN (20,000 IU) on the day of virus infection. These findings indicate the need for evaluation of low-dose use of oral IFN in the development of improved clinical therapies for the treatment of cardiovascular disease.