Prior airway exposure to allergen increases virus-induced airway hyperresponsiveness

Abstract

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in early life can lead to changes in airway function, but there are likely additional predisposing factors, such as prior allergen exposure, determining which children develop wheezing and asthma. OBJECTIVE: To define the effects of prior airway exposure to sensitizing allergen on the development of airway inflammation and hyperresponsiveness (AHR) to subsequent RSV infection. METHODS: BALB/c mice were exposed to ovalbumin or PBS exclusively through the airways and subsequently infected with RSV or sham-inoculated. AHR, lung inflammation, and the frequency of cytokine-producing T lymphocytes in the lung were determined. RESULTS: In PBS-exposed mice, RSV infection induced AHR and an increased proportion of TH1-type (IFN-gamma and IL-12) cytokine-producing cells in the lungs. However, in mice previously exposed to ovalbumin through the airways and subsequently infected with RSV, the degree of AHR was significantly increased and was associated with an increased proportion of TH2 (IL-4, IL-5) cytokine-producing T lymphocytes. This response was also associated with an increased accumulation of eosinophils, neutrophils, and CD8+ T cells in the lungs. CONCLUSIONS: These data suggest that prior airway exposure to allergen may predispose sensitized hosts to a greater degree of altered airway function upon subsequent respiratory viral infection.