Efficacy and safety of orally/sublingually, intranasally, and intraperitoneally administered recombinant murine interferon in the treatment of murineencephalomyocarditis virus

Interferons (IFN) have been shown to be effective in protecting animals aga inst lethal viral infections when administered systemically in relatively h igh doses. Intraperitoneal (i.p.) injection of mice with encephalomyocardit is virus (EMCV) gives rise to a rapidly progressive fatal disease character ized by central nervous system involvement and encephalitis. IFN-alpha has been shown to be effective in protecting mice against lethal EMCV infection when given via parenteral and oral/sublingual routes. The current study wa s designed to explore the ability of orally/sublingually and intranasally ( i.n.) administered IFN-alpha to treat mice infected with EMCV in support of a planned clinical trial to evaluate efficacy of oral IFN-alpha in human v iral infections. The primary objective of the study was to determine the ef ficacy of recombinant murine IFN-alpha (rMuIFN-alpha) in the treatment of m ice infected with 100 LD50 EMCV following oral, i.n., and i.p. administrati on at doses of 20,000 and 100, 000 IU. The results of the current experimen t did not indicate protection from infection with EMCV in mice that receive d IFN by the i.n. or oral/sublingual routes. The negative controls, infecti on of mice with 100 LD50 of EMCV followed by treatment with excipient via a ll three routes, resulted in death of nearly all mice, as expected. The pos itive control, treatment of EMCV-infected (100 LD50) mice with rMuIFN-alpha via the i.p. route, was successful in protecting a significant number of m ice from death compared with matched controls. This study points out the ne ed to determine the optimum conditions for administration of oral/sublingua l or i.n. IFN to insure maximum efficacy against viral infections.