Persistence of airway hyperresponsiveness in mice infected with influenza as infants
Early life exposure to viral lower respiratory illness is thought to exacerbate the development of allergic airways disease such as asthma. There are few published murine models of respiratory virus infection in infants and neonates. This study aimed to characterize the inflammatory and physiological pattern of Influenza A infection in infant mice.
Methods: Infant BALB/c mice were inoculated on day 7 (d7) with 10mL 103.8 pfu Influenza virus A/Mem/1/71 (H3N1) or media control. Bronchoalveolar lavage fluid was collected at d1-5, 7, 10, 14 & 21 post-inoculation to determine the inflammatory profile. Following the establishment of peak inflammation and clearance, physiology was assessed during the acute inflammatory period (d5-post-inoculation) and resolution of infection (d21) using a small animal ventilator and a modification of the forced oscillation technique. The Constant Phase Model was fitted to Respiratory Impedance data to produce airway and tissue mechanics. Airway hyperresponsiveness (AHR) was assessed to inhaled methacholine (MCh) (0.01–30 mg/mL) at d21.
Results: Cellular inflammation peaked at d3 in Influenza infected mice (1.23 ¥ 106 (0.23) cells/mL) compared to control animals (2.79 ¥ 105 (0.29) cells/mL; p = 0.007) and had resolved to control levels by d14 (1.65 ¥ 105 (0.48) cells/mL vs 1.53 ¥ 105 (0.22) cells/mL; p = 0.837). Mice infected with Influenza A virus showed changes to baseline mechanics at d5, and AHR to inhaled MCh (p = 0.01) at d21 compared to control animals.
Conclusions: These findings confirm that Influenza A virus induces significant changes in baseline mechanics during acute infection in infant mice, and that AHR persists beyond the resolution of inflammation.
History
Publication title
RespirologyVolume
13 (Suppl.2)Editors
P BardinPagination
A26ISSN
1323-7799Department/School
Tasmanian School of MedicinePublisher
Wiley-Blackwell Publishing AsiaPlace of publication
AustraliaEvent title
Thoracic Society of Australia and New Zealand Annual Scientific Meeting 2008Event Venue
Melbourne, AustraliaDate of Event (Start Date)
2008-03-28Date of Event (End Date)
2008-03-31Repository Status
- Restricted