inosinic-acid and Orthomyxoviridae-Infections

An inbred murine model (BALB/c) was utilized to assess the protective effect of the immunomodulator methyl inosine 5'-monophosphate (MIMP) against infection with influenza A/PR/8/34 (H1N1) virus. Contrary to the data reported for outbred mice (NMRI) infected with the aerosolized virus (Masihi, Hadden, 2003. J. Int. Immunopharmacol. 3, 1205-1215), there were no improvements in the outcomes of infection in the inbred animals treated with MIMP intranasally 1 day before the challenge and/or orally after the challenge for 5 days (up to 10 mg/kg/day). Nevertheless, complete protection against lethality was afforded by the treatment with the neuraminidase inhibitor peramivir given once daily for 5 days after the challenge (10 mg/kg/day). We speculate that the rapid progression of the disease in inbred mice caused by the intranasal challenge may render the MIMP-treatment ineffective. Our results emphasize the need for careful consideration of murine strains and routes of virus challenge in the design of experiments utilizing lethal influenza virus infection.

Topics: Acids, Carbocyclic; Age Factors; Animals; Antiviral Agents; Body Weight; Cyclopentanes; Disease Models, Animal; Female; Guanidines; Influenza A Virus, H1N1 Subtype; Inosine Monophosphate; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections

Methyl inosine monophosphate (MIMP) is a novel thymomimetic purine immunomodulator capable of enhancing a wide variety of immune responses. Intravenous (i.v.) administration of MIMP 1 day prior to influenza virus infection could confer partial protection and significantly increase the mean survival of treated mice. Intranasal (i.n.) administration of MIMP improved survival rates and incorporation of MIMP in squalane-saline emulsion 1 day prior to or 1 h after influenza infection conferred complete protection. Mice administered MIMP had reduced levels of lung virus and lower titers of circulating serum hemagglutination-inhibition (HI) antibodies. Complete survival and reduction of viral load after influenza challenge infection suggests effective stimulation by MIMP of protective responses against influenza virus.

Topics: Aerosols; Animals; Female; Influenza A virus; Inosine Monophosphate; Mice; Orthomyxoviridae Infections; Survival Rate