Efficacy and safety of orally/sublingually, intranasally, and intraperitoneally administered recombinant murine interferon in the treatment of murine encephalomyocarditis virus.
Interferons (IFN) have been shown to be effective in protecting animals against lethal viral infections when administered systemically in relatively high doses. Intraperitoneal (i.p.) injection of mice with encephalomyocarditis virus (EMCV) gives rise to a rapidly progressive fatal disease characterized 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 was 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 viral infections. The primary objective of the study was to determine the efficacy of recombinant murine IFN-alpha (rMuIFN-alpha) in the treatment of mice infected with 100 LD(50) EMCV following oral, i.n., and i.p. administration at doses of 20,000 and 100,000 IU. The results of the current experiment did not indicate protection from infection with EMCV in mice that received IFN by the i.n. or oral/sublingual routes. The negative controls, infection of mice with 100 LD(50) of EMCV followed by treatment with excipient via all three routes, resulted in death of nearly all mice, as expected. The positive control, treatment of EMCV-infected (100 LD(50)) mice with rMuIFN-alpha via the i.p. route, was successful in protecting a significant number of mice from death compared with matched controls. This study points out the need to determine the optimum conditions for administration of oral/sublingual or i.n. IFN to insure maximum efficacy against viral infections.
Sonnenfeld
G
G
Department of Microbiology Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA. sonneng@msme.edu
Tovey
M
M
Schellekens
H
H
Kinney
K S
KS
Belay
T
T
Morton
D S
DS
Austin
C E
CE
Reitman
M
M
Fong
T A
TA
Vaughan
H S
HS
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D018188:Cardiovirus Infections / Q000188:drug therapy* / Q000401:mortality; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004686:Encephalomyocarditis virus / Q000187:drug effects*; D005260:Female; D007274:Injections, Intraperitoneal; D007370:Interferon Type I / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D007928:Lethal Dose 50; D051379:Mice; D011897:Random Allocation; D011994:Recombinant Proteins; D017186:Titrimetry
D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins