ATTENUATION OF ALLERGIC AIRWAY INFLAMMATION IN IL-4 DEFICIENT MICE

To investigate the role of IL-4 in vivo in allergic asthma, we develop ed a murine model of allergen-induced airway inflammation. Repeated da ily exposure es of actively immunized C57BL/6 mice to aerosolized oval bumin (OVA) induced a peribronchial inflammation and an increase in eo sinophils and lymphocytes in bronchoalveolar-lavage (BAL) fluid. In IL -4 deficient (IL4(-/-)) mice, treated in the same way, there were subs tantially fewer eosinophils in BAL and much less peribronchial inflamm ation compared with wild type mice. In this model, mast cell deficient (W/W-v) mice developed a similar degree of BAL eosinophilia and perib ronchial inflammation as wild type mice, demonstrating that the mast c ell is not required for the induction of chronic airway inflammation. In contrast, BAL eosinophilia and airway inflammation were absent in O VA-treated MHC ClassII deficient (B6.Aa(-/-)) mice which lack mature C D4+ T lymphocytes. In conclusion, these results indicate that IL-4 is a central mediator of allergic airway inflammation, regulating antigen -induced eosinophil recruitment into the airways by a T cell dependent mechanism.