ALLERGEN-INDUCED AIRWAY INFLAMMATION AND BRONCHIAL RESPONSIVENESS IN WILD-TYPE AND INTERLEUKIN-4-DEFICIENT MICE

T helper 2 (Th2)-like cytokines are thought to play a crucial role in the pathogenesis of airway inflammation in atopic asthma, leading to b ronchial hyperresponsiveness. To investigate the role of the principal Th2 cytokine interleukin-4 (IL-4) in asthma, we examined the allergen -induced changes in airway morphology and bronchial responsiveness (BR ) in an in vivo mouse model. C57BL/6 mice were actively sensitized to ovalbumin (OVA) and exposed daily to aerosolized OVA or saline (SAL) f or 7 days. Twenty-four hours after the last allergen exposure, total a nd differential counts of bronchoalveolar lavage cells revealed a sign ificant increase of eosinophils and lymphocytes in OVA-exposed immuniz ed mice compared with SAL-exposed animals. In IL-4-deficient (IL-4(-/- )) mice, treated in the same way, there were substantially fewer eosin ophils in bronchoalveolar lavage compared with wild-type mice. Allerge n exposure of actively sensitized wild-type mice induced a significant increase of BR to carbachol and to serotonin compared with SAL-expose d mice. In contrast, OVA exposure of immunized IL-4(-/-) mice did not augment BR to serotonin compared with SAL-challenged IL-4(-/-) mice. I n conclusion, these data indicate that repeated allergen exposure in s ensitized mice induces airway inflammation and bronchial hyperresponsi veness, and that IL-4 plays a predominant role in the pathogenesis of both phenomena.