IL-5 and eosinophils are essential for the development of airway hyperresponsiveness following acute respiratory syncytial virus infection.
Acute Disease, Animal, Bronchial Hyperreactivity/*etiology, Eosinophils/*physiology, Female, Integrins/physiology, Interferon Type II/biosynthesis, Interleukin-5/*physiology, Methacholine Chloride/pharmacology, Mice, Mice, Inbred C57BL, Receptors, Lymphocyte Homing/physiology, Respiratory Syncytial Virus Infections/*physiopathology
J Immunol 1999 Mar 1;162(5):2997-3004
HL36577/HL/NHLBI, HL61005/HL/NHLBI, AI30389/AI/NIAID
Viral respiratory infections can cause bronchial hyperresponsiveness and exacerbate asthma. In mice, respiratory syncytial virus (RSV) infection, which induces an immune response dominated by IFN-gamma, results in airway hyperresponsiveness (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 eosinophilia, we tested the ability of mice deficient in each of these cytokines 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 production of IFN-gamma, IL-4, and IL-5 by mononuclear cells from peribronchial lymph nodes were monitored. RSV infection resulted in airway eosinophilia and 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 responses and enhanced the responses in IL-4-deficient mice. Anti-VLA-4 (very late Ag-4) treatment prevented lung eosinophilia and AHR following RSV infection and IL-5 reconstitution. We conclude that in response to RSV, IL-5 is essential for the influx of eosinophils into the lung and that eosinophils in turn are critical for the development of AHR. IFN-gamma and IL-4 are not essential for these responses to RSV infection.
Schwarze, J; Cieslewicz, G; Hamelmann, E; Joetham, A; Shultz, L D.; Lamers, M C.; and Gelfand, E W., " IL-5 and eosinophils are essential for the development of airway hyperresponsiveness following acute respiratory syncytial virus infection." (1999). Faculty Research 1990 - 1999. 1226.