Physiological and immunological responses to allergen in three strains of mouse

There is a range of epidemiological data suggesting a link between viral lower respiratory illness in early life and long-term symptoms such as wheeze and asthma. Whether this relationship is the result of viral-specific or host-response factors is unclear. We recently found BALB/c mice infected with RSV are hyper-responsive to inhaled (i.h.) but not intravenous (i.v.) MCh in vivo. The aim of this study is to determine how Influenza A infection influences the pattern of airway hyper-responsiveness in mice.

Methods: Female BALB/c mice at 8 wks were inoculated with 50µL 104.5 pfu Influenza virus A/Mem/1/71(H3N1) or media control under light anaesthesia. Physiology was assessed during peak viral titre (d4 postinoculation) and resolution of infection (d20) using a small animal ventilator and a modification of the forced oscillation technique. The Constant Phase Model was fitted to Respiratory Impedance (Zrs) data to produce airway (Raw) and tissue (G,H) parameters. Responsiveness was assessed to both i.h. MCh (0.01–10 mg/mL) and i.v. MCh (6–96µg/min/kg). Lavage fluid was collected to assess inflammation and cytokines. MCh responsiveness in vitro was also assessed at the same time-points using tracheal rings.

Results: Mice infected with Influenza A virus Mem/1/71 are hyperresponsive to both i.h. (P = 0.027) and i.v. (P = 0.015) MCh compared to control animals at d4, but not at d20 (i.h. P = 0.633; iv P = 0.755). In vitro responses of tracheal rings to MCh challenge were not altered by Influenza A infection. During peak viral load, cellular inflammation was elevated in Influenza infected mice (6.98 × 105 cells/mL) compared to control animals (1.62 × 105 cells/mL; P = 0.018) and had returned to baseline levels by d20.

Conclusions: These findings confirm that Influenza A virus, in agreement with RSV, induce AHR during acute phase infection in mice. However, the pattern of responsiveness between the viruses is different.