Inhaled dexamethasone differentially attenuates disease relapse and established allergic asthma in mice

Abstract

Inhaled glucocorticoids are effective in patients with chronic allergic asthma. We examined the effects of inhaled glucocorticoids on relapse (allergen challenge after disease remission) and established/overt allergic asthma (repeated allergen challenge in weekly intervals) in mice to establish a reference standard for novel treatments. BALB/c mice were treated before relapse or during overt disease with 1 h of nebulized PBS or 10 mg% dexamethasone twice daily for 5 days. Dexamethasone eliminated airway hyperresponsiveness before relapse and during overt disease. They more efficiently reduced airway inflammation, mucus production, and OVA-specific IgG1 and IgE during relapse compared to overt disease. However, during overt disease, parenchymal inflammatory infiltrates were more effectively eliminated compared to relapse, suggesting that activated infiltrating leukocytes have increased sensitivity to steroids. These data demonstrate that inhaled corticosteroids attenuate relapse and overt disease differentially and suggest that both airway and parenchymal inflammation need to be evaluated for treatment efficacy.