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 bronchial 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) for 7 days. Twenty-four hours after the last allergen exposure, total and differential counts of bronchoalveolar lavage cells revealed a significant increase of eosinophils and lymphocytes in OVA-exposed immunized mice compared with SAL-exposed animals. In IL-4-deficient (IL-4-/-) mice, treated in the same way, there were substantially fewer eosinophils in bronchoalveolar lavage compared with wild-type mice. Allergen exposure of actively sensitized wild-type mice induced a significant increase of BR to carbachol and to serotonin compared with SAL-exposed mice. In contrast, OVA exposure of immunized IL-4-/- mice did not augment BR to serotonin compared with SAL-challenged IL-4-/- mice. In conclusion, these data indicate that repeated allergen exposure in sensitized mice induces airway inflammation and bronchial hyperresponsiveness, and that IL-4 plays a predominant role in the pathogenesis of both phenomena.