title: Acute Influenza A infection induces bronchial hyper-responsiveness in mice.
abstract: 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.
authors.affiliation: Division of Clinical Sciences, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, PO Box 855, West Perth WA 6872, Australia. lizb@ichr.uwa.edu.au
authors.forename: E M
authors.initials: EM
authors.lastname: Bozanich
authors.forename: R C
authors.initials: RC
authors.lastname: Gualano
authors.forename: G R
authors.initials: GR
authors.lastname: Zosky
authors.forename: A N
authors.initials: AN
authors.lastname: Larcombe
authors.forename: D J
authors.initials: DJ
authors.lastname: Turner
authors.forename: Z
authors.initials: Z
authors.lastname: Hantos
authors.forename: P D
authors.initials: PD
authors.lastname: Sly
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000209:etiology*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D002452:Cell Count / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005260:Female; D066298:In Vitro Techniques; D009980:Influenza A virus; D007252:Influenza Vaccines / Q000008:administration & dosage; D008168:Lung / Q000821:virology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000150:complications*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000209:etiology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016085:Bronchoconstrictor Agents; D016207:Cytokines; D007252:Influenza Vaccines; D042461:Vascular Endothelial Growth Factor A; D016210:Methacholine Chloride; D015232:Dinoprostone