ALLERGEN-INDUCED BRONCHIAL HYPERREACTIVITY AND EOSINOPHILIC INFLAMMATION OCCUR IN THE ABSENCE OF IGE IN A MOUSE MODEL OF ASTHMA

In patients with asthma, elevations of IgE correlate both with allergi c inflammation of the airways and with bronchial hyperreactivity (BHR) , Several investigations, using mouse models of this disease, have ind icated a central role for IgE in the pathogenesis of the eosinophilic inflammation as well as in the obstructive airway physiology of BHR. S ome diagnostic studies and therapeutic strategies for asthma are based on the putative role of IgE in asthma pathogenesis. Here, we use mice with a null mutation of the C epsilon locus to show that bronchial in flammation and BHR in response to allergen inhalation both can occur i n the absence of IgE, We demonstrate that the eosinophilic bronchial i nflammation elicited in an established mouse model of hypersensitivity to Aspergillus fumigatus (Af) is accompanied by the asthmatic physiol ogy of BHR. Wild-type and IgE-deficient mice were sensitized intranasa lly with Af extract, Both groups of animals developed bronchoalveolar lavage eosinophilia and pulmonary parenchymal eosinophilia, This was a ccompanied by increased serum Levels of total and Af-specific IgE in t he wild-type animals only, This Af-sensitization protocol resulted in significant BHR in both wild-type mice and IgE-deficient mice, Interes tingly, unsensitized IgE-deficient mice had increased bronchial respon siveness compared with unsensitized wildtype controls, We conclude tha t BHR and airways inflammation can be fully expressed via IgE-independ ent mechanisms. These may involve the activation of mast cells by fact ors other than IgE as well as a mucosal lymphocyte-mediated immune res ponse to allergen.