RESPIRATORY SYNCYTIAL VIRUS-INFECTION RESULTS IN AIRWAY HYPERRESPONSIVENESS AND ENHANCED AIRWAY SENSITIZATION TO ALLERGEN

Viral respiratory infections can predispose to the development of asth ma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is as sociated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen, We demonstrate that acute vi ral infection results in increased airway responsiveness to inhaled me thacholine and pulmonary neutrophilic and eosinophilic inflammation, T his response is associated with predominant production of Th-l-type cy tokines in peribronchial lymph node cells in vitro, Mice sensitized to ovalbumin via the airways after RSV infection developed increased air way responsiveness to methacholine and pulmonary eosinophilic and neut rophilic inflammation, associated with the predominant production of T h-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abol ished ah-way hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection, We conclude that RSV infection results in airway hyperrespo nsiveness in the acute phase and leads to changes in immune function t hat can enhance the effects of airway sensitization to antigen after i nfection, Ln both situations, airway hyperresponsiveness is closely as sociated with pulmonary eosinophilic inflammation, This model provides a means for further analyzing the influence of viral respiratory infe ctions on airway sensitization and the development of altered airway r esponsiveness.