Inhaled nitric oxide therapy fails to improve outcome in experimental severe influenza

Int J Med Sci. 2012;9(2):157-62. doi: 10.7150/ijms.3880. Epub 2012 Jan 13.

Abstract

In vitro, nitric oxide (NO) has been shown to have antimicrobial activity against a wide range of viruses, including influenza A virus. Therefore, we hypothesized that inhaled nitric oxide (iNO) would increase survival in vivo by reducing the viral load in C57Bl/6 mice infected with a lethal dose of influenza A/WSN/33 (H1N1; WSN/33) virus. NO was delivered to influenza-infected mice either continuously or intermittently at 80 or 160 ppm, respectively, using both prophylactic and post-infection treatment strategies. Murine survival and weight loss were assessed, and lung viral load was quantified via plaque assay. Here, we report that iNO administered prophylactically or post-influenza infection failed to improve survival of infected mice. No difference in lung viral load was observed between experimental groups. Although NO has antiviral activity against influenza A virus in vitro, iNO therapy provided no apparent benefit when used for treatment of influenza A virus infection in vivo.

Keywords: influenza A/WSN/33; nitric oxide; severe influenza.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Dogs
  • Drug Evaluation, Preclinical
  • Female
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Influenza A Virus, H1N1 Subtype / physiology
  • Lung / drug effects
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / administration & dosage*
  • Nitric Oxide / adverse effects
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Severity of Illness Index
  • Treatment Failure
  • Viral Load / drug effects

Substances

  • Nitric Oxide