SYNERGISTIC EFFECTS OF TACROLIMUS AND HUMAN INTERFERON-ALPHA A D IN MURINE VIRAL MYOCARDITIS/

The effects of interferon-alpha A/D (IFN) therapy in combination with various immunosuppressants were investigated in a murine model of vira l myocarditis. Viral infection is an important cause of morbidity in i mmunocompromised hosts and transplant recipients. Human IFN therapy re duces viral replication, reducing the virus-induced myocardial destruc tion, Groups consisting of 25 C3H/He mice received i.p. injections of prednisolone, azathioprine, 15-deoxyspergualin, cyclosporine or tacrol imus (FK506), for 16 days beginning 2 days before inoculation with 500 plaque-forming units of encephalomyocarditis virus (EMCV). IFN, 10(4) U/g daily, was administered i.p, alone or in combination with immunos uppressants to separate groups of mice beginning on the day of viral i noculation. Animals were sacrificed at random at 4 or 10 days after in oculation with EMCV. The survival rate was significantly higher in mic e treated with azathioprine, 15-deoxyspergualin, cyclosporine or FK506 in combination with IFN than in infected controls (P < .01) and was s imilar to the rate in the IFN monotherapy group. Survival in mice trea ted with prednisolone resembled that in infected controls and was sign ificantly lower than in mice treated with IFN (P < .01). Heart weight was lower and cellular infiltration in the myocardium was reduced in m ice treated with both FK506 and IFN compared with mice given IFN monot herapy. The results suggest that the effect of IFN therapy in viral my ocarditis differs depending on which immunosuppressants is used. The f indings suggest that the combination of FK506 and IFN may have benefic ial effects in hosts with viral myocarditis by reducing cellular infil tration of heart.