DEVELOPMENT OF AIRWAY HYPERRESPONSIVENESS IS DEPENDENT ON INTERFERON-GAMMA AND INDEPENDENT OF EOSINOPHIL INFILTRATION

In this study the role of interleukin (IL)4, IL5, interferon (IFN)gamm a, and tumor necrosis factor (TNF)alpha in the development of airway h yperresponsiveness and inflammatory cell infiltration was investigated using a murine model for allergic asthma. Mice were sensitized with o valbumin and subsequently challenged repeatedly with ovalbumin aerosol s. During the challenge period, mice were treated with monoclonal anti bodies directed against IL4, IL5, IFN gamma, or TNF alpha. Control ant ibody-treated mice showed airway hyperresponsiveness to methacholine a nd the presence of eosinophils in bronchoalveolar lavage (BAL). Treatm ent with antibodies to IFN gamma completely abolished development of a irway hyperresponsiveness in ovalbumin-challenged animals. After treat ment with antibodies to TNF alpha, airway hyperresponsiveness in the o valbumin-challenged animals was partially but not significantly inhibi ted. Antibodies to IL4 or IL5 did not inhibit airway hyperresponsivene ss. The presence of eosinophils in BAL of ovalbumin-challenged mice wa s completely inhibited after treatment with antibodies to IL5. Treatme nt with antibodies to IL4, IFN gamma, or TNF alpha had no effect on eo sinophilia. Because IFN gamma and IL5 have either an effect on the ind uction of airway hyperresponsiveness or on the development of eosinoph il infiltration, our results suggest that the two phenomena are differ entially regulated.