AN IMPROVED MURINE MODEL OF ASTHMA - SELECTIVE AIRWAY INFLAMMATION, EPITHELIAL LESIONS AND INCREASED METHACHOLINE RESPONSIVENESS FOLLOWING CHRONIC EXPOSURE TO AEROSOLIZED ALLERGEN

Background-Existing murine models of asthma lack many of the inflammat ory and epithelial changes that are typical of the human disease. More over, these models are frequently complicated by allergic alveolitis. Methods-High IgE responder BALB/c mice were systemically sensitised to ovalbumin and chronically challenged with low particle mass concentra tions of aerosolised ovalbumin. Titres of anti-ovalbumin IgE in serum were measured at two weekly intervals by enzyme immunoassay, accumulat ion of inflammatory cells and histopathological abnormalities of the e pithelium were quantified morphometrically in the trachea and the lung s, and airway reactivity was assessed by measuring bronchoconstriction following intravenous administration of methacholine. Results-Mice se nsitised by two intraperitoneal injections of ovalbumin developed high titres of IgE antibodies to ovalbumin. Following exposure to low conc entrations of aerosolised antigen for up to eight weeks these animals developed a progressive inflammatory response in the airways, characte rised by the presence of intraepithelial eosinophils and by infiltrati on of the lamina propria with lymphoid/ mononuclear cells, without ass ociated alveolitis. Goblet cell hyperplasia/ metaplasia was induced in the intrapulmonary airways, while epithelial thickening and subepithe lial fibrosis were evident following chronic exposure. In parallel, th e mice developed increased sensitivity to induction of bronchospasm, a s well as increased maximal reactivity. Non-immunised mice exposed to aerosolised ovalbumin had low or absent anti-ovalbumin IgE and did not exhibit inflammatory or epithelial changes, but developed airway hype rreactivity. Conclusions-This experimental model replicates many of th e features of human asthma and should facilitate studies of pathogenet ic mechanisms and of potential therapeutic agents.