Am. J. Respir. Crit. Care Med., Volume 162, Number 2, August 2000, 380-386

Critical Roles for Interleukin-4 and Interleukin-5 during Respiratory Syncytial Virus Infection in the Development of Airway Hyperresponsiveness after Airway Sensitization

JÜRGEN SCHWARZE, GRZEGORZ CIESLEWICZ, ANTHONY JOETHAM, TOSHIHIDE IKEMURA, MIKA J. MÄKELÄ, AZZEDDINE DAKHAMA, LEONARD D. SHULTZ, MARINUS C. LAMERS, and ERWIN W. GELFAND

Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; Jackson Laboratory, Bar Harbor, Maine; and Max-Planck-Institut für Immunbiologie, Freiburg, Germany

In mice, respiratory syncytial virus (RSV) infection can enhance the consequences of allergic airway sensitization, resulting in lung eosinophilia and the development of airway hyperresponsiveness (AHR) to inhaled methacholine (MCh). To delineate a role for interleukin-5 (IL-5), interleukin-4 (IL-4), and interferon gamma (IFN-) in mediating the effects of RSV infection on subsequent allergic sensitization, we treated BALB/c mice with anti-IL-5 during acute RSV infection but not during subsequent exposure to ovalbumin (OVA). IL-5-deficient and IL-4-deficient mice were also treated with IL-5 either during acute RSV infection or during the sensitization period. Airway responsiveness to inhaled MCh was assessed and numbers of lung eosinophils 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 allergen exposure were also markedly reduced. IL-5 administration during RSV infection restored the responses to allergen in both IL-5- and IL-4-deficient mice. However, IL-5 administration only during sensitization restored these responses in IL-4-deficient but not in IL-5-deficient animals. IFN--deficient mice developed AHR and some lung eosinophilia after allergen exposure 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 allergic airway sensitization, resulting in the development of AHR and lung eosinophilia.

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