title: Inhaled nitric oxide therapy fails to improve outcome in experimental severe influenza.
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.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Canada.
authors.forename: Ilyse
authors.initials: I
authors.lastname: Darwish
authors.forename: Chris
authors.initials: C
authors.lastname: Miller
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D012720:Severity of Illness Index; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D009569:Nitric Oxide