IL-5 and eosinophils are essential for the development of airway hyperresponsiveness following acute respiratory syncytial virus infection

Viral respiratory infections can cause bronchial hyperresponsiveness and ex acerbate asthma. In mice, respiratory syncytial virus (RSV) infection, whic h induces an immune response dominated by IFN-gamma, results in airway hype rresponsiveness (AHR) and eosinophil influx into the airways, both of which are prevented by pretreatment with anti-IL-5 Ab, To delineate the role of IL-5, IL-4, and IFN-gamma in the development of RSV-induced AHR and lung eo sinophilia, we tested the ability of mice deficient in each of these cytoki nes to develop these symptoms of RSV infection. Mice deficient in either IL -5, IL-4, or IFN-gamma were administered infectious RSV intranasally, and 6 days later, airway responsiveness to inhaled methacholine was assessed by barometric body plethysmography, and numbers of lung eosinophils and produc tion of IFN-gamma, IL-4, and IL-5 by mononuclear cells from peribronchial l ymph nodes were monitored. RSV infection resulted in airway eosinophilia an d AHR in both IL-4- and IFN-gamma-deficient mice, but not in IL-5-deficient mice. Reconstitution of IL-5-deficient mice with IL-5 restored these respo nses and enhanced the responses in IL-4-deficient mice, Anti-VLA-4 (very la te Ag-4) treatment prevented lung eosinophilia and AHR following RSV infect ion and IL-5 reconstitution. We conclude that in response to RSV, IL-5 is e ssential for the influx of eosinophils into the lung and that eosinophils i n turn are critical for the development of AHR. IFN-gamma and IL-4 are not essential for these responses to RSV infection.