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Rationale:Prior studies revealed an increased eosinophilic inflammation and airway hyperrespnsiveness (AHR) after repeated allergen instillation into the nose of A/J mice, whereas these responses progressively reduced in 3 other mouse strains. Because of this unique sensitiveness of A/J mice, these animals were used here to assess the efficacy of glucocorticoid (GC) treatment on the progression of the inflammatory response in a short−term model of asthma. Methods: Mice of strain A were sensitized and boosted with a mixture of Al(OH)3 and ovalbumin (OVA), and challenged for 2 or 4 consecutive days starting from day 19 post−sensitization. Treatments with dexamethasone (DEX, 3 mg/kg, oral), or vehicle, were done 1 h before provocation. Invasive and non−invasive methodologies were employed for measurement of AHR. BAL fluids and lung sections were examined for quantification of the inflammatory status, mucus and fibrogenesis. IL−4, IL−13 and eotaxin levels were measured in the lung tissue by ELISA. Results: We found that the two−provocation regimen was active in causing AHR, eosinophilic inflammation, mucus production and fibrogenesis, all of which being clearly sensitive to DEX. As expected, these changes were intensified in those animals subjected to four allergen provocations. DEX remained active in preventing the eosinophil accumulation of BAL fluid samples but failed to alter tissue eosinophilia. Similarly, AHR, increased generation of IL−4, IL−13, eotaxin and fibrogenesis also appeared sensitive to DEX in case of two but not four OVA provocations. Conclusion: These findings show that the actively A/J mouse sub−strain develops asthma−like pathological changes, including AHR and tissue remodeling, which are progressively resistant to GC treatment. We postulate that this model may be a useful approach for studying glucocorticoid resistance and asthma in the mouse. This abstract is funded by: CNPq and FAPERJ. Am J Respir Crit Care Med 179;2009:A4274 Internet address: www.atsjournals.org Online Abstracts Issue