Acute Influenza A infection induces bronchial hyper-responsiveness in mice

Respir Physiol Neurobiol. 2008 Aug 31;162(3):190-6. doi: 10.1016/j.resp.2008.06.011. Epub 2008 Jun 20.


This study aimed to determine whether the route of administration of methacholine (MCh) influenced the pattern of airway hyper-responsiveness (AHR) in mice. BALB/c mice were inoculated with a 50-microL volume containing 10(4.5)-pfu Influenza virus A/Mem/1/71(H3N1) or media. MCh responsiveness in vivo [inhaled (0.01-30 mg/mL), i.v. MCh (6-48 microg/min/kg)] and in vitro were measured at day 4 post-infection (D4) during acute lower respiratory infection (LRI) and following resolution of infection at day 20 (D20) using a low-frequency, forced oscillation technique. Inflammation was assessed in bronchoalveolar lavage fluid. Infected mice had pulmonary inflammation and heightened responsiveness to both inhaled (p<0.03) and intravenous (p<0.02) MCh on D4, but not on D20. In vitro responsiveness was not altered at either time point. Influenza A LRI results in AHR during acute infection associated with a marked inflammatory response and increased permeability of the alveolar-capillary barrier. These data suggest that intrinsic muscle properties are not altered but MCh has greater access to airway smooth muscle during acute infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Bronchial Hyperreactivity / drug therapy
  • Bronchial Hyperreactivity / etiology*
  • Bronchoconstrictor Agents / administration & dosage
  • Cell Count / methods
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Female
  • In Vitro Techniques
  • Influenza A virus*
  • Influenza Vaccines / administration & dosage
  • Lung / virology
  • Methacholine Chloride / administration & dosage
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / complications*
  • Respiratory Hypersensitivity / drug therapy
  • Respiratory Hypersensitivity / etiology*
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism


  • Bronchoconstrictor Agents
  • Cytokines
  • Influenza Vaccines
  • Vascular Endothelial Growth Factor A
  • Methacholine Chloride
  • Dinoprostone