Critical roles for interleukin-4 and interleukin-5 during respiratory syncytial virus infection in the development sf airway hyperresponsiveness after airway sensitization

In mice, respiratory syncytial virus (RSV) infection can enhance the conseq uences of allergic airway sensitization, resulting in lung eosinophilia and the development of airway hyperresponsiveness (AHR) to inhaled methacholin e (MCh). To delineate a role for interleukin-5 (IL-5), interleukin-4 (IL-4) , and interferon gamma (IFN-gamma) in mediating the effects of RSV infectio n on subsequent allergic sensitization, we treated BALB/c mice with anti-IL -5 during acute RSV infection but not during subsequent exposure to ovalbum in (OVA). IL-5-deficient and IL-deficient mice were also treated with IL-5 either during acute RSV infection or during the sensitization period. Airwa y responsiveness to inhaled MCh was assessed and numbers of lung eosinophil s were monitored. Anti-IL-5 treatment during RSV infection reduced AHR and lung eosinophilia after subsequent exposure to allergen. In IL-5-deficient or IL-4-deficient mice lung eosinophilia and AHR after RSV infection and al lergen exposure were also markedly reduced. IL-5 administration during RSV infection restored the responses to allergen in both IL-5- and IL-4-deficie nt mice. However, IL-5 administration only during sensitization restored th ese responses in IL-4-deficient but not in IL-5-deficient animals. IFN-gamm a-deficient mice developed AHR and some lung eosinophilia after allergen ex posure alone and when RSV infection preceded allergen, these responses were enhanced. We conclude that both IL-5, particularly during acute infection, and IL-4 are critical in mediating the effects of RSV infection on allergi c airway sensitization, resulting in the development of AHR and lung eosino philia.