A MURINE MODEL OF ALLERGIC RHINITIS - STUDIES ON THE ROLE OF IGE IN PATHOGENESIS AND ANALYSIS OF THE EOSINOPHIL INFLUX ELICITED BY ALLERGENAND EOTAXIN

Background: Allergic rhinitis is a prevalent disease with significant morbidity, Studies of its pathophysiology in human subjects have been limited. Nasal biopsy specimens are difficult to obtain, and nasal sec retions incompletely reflect the cellular and molecular events in the mucosa, IgE-mediated mast cell activation and the elaboration of facto rs promoting eosinophil development and chemotaxis are likely to parti cipate in pathogenesis. Objectives: We sought to develop a murine mode l of allergic rhinitis, to use it to assess the role of IgE in pathoge nesis, and to study the effects of IL-5 and eotasin in the nasal mucos a, Methods: A protein extract of Aspergillus fumigatus (Af) was instil led intranasally in mice. Histologic changes were examined in wild-typ e and IgE-deficient (IgE(-/-)) animals. The effect of eotasin administ ration was assessed in wild-type and IL-5 transgenic mice. Results: Af -treated mice developed a nasal mucosal eosinophil influx comparable t o that described for humans, This histology was distinct from that obs erved in a murine model Af-induced asthma, The pathology appeared over a time course similar to that reported for human subjects. There was no difference in the intensity of the mucosal inflammatory infiltrate of rif-treated IgE(-/-) mice compared with wild-type mice. Eotaxin mas able to recruit eosinophils to the mucosa but only in IL-5 transgenic animals, Conclusion: We describe a murine model for allergic rhinitis with an eosinophilic infiltrate comparable to that found in human dis ease and have demonstrated that rhinitis can arise in the absence of I gE, We have shown that the eosinophil influx can be induced by eotaxin in the presence of IL-5.