Airway subepithelial fibrosis in a murine model of atopic asthma - Suppression by dexamethasone or anti-interleukin-5 antibody

Fibrosis in the reticular layer beneath the epithelial basement membrane Is a feature of airway remodeling in human asthma, We previously reported the presence of subepithelial fibrosis (SEF) in a disease model of atopic asth ma in which mice were sensitized and intratracheally challenged with ovalbu min (OVA) (Blyth and colleagues, Am. J. Respir. Cell Mol. Biol, 1996;14:425 -438), Here, we describe further studies to quantify the degree of SEF afte r its induction by repeated exposure of the airways to allergen. The amount of subepithelial reticulin in the airways of animals challenged three time s with 80 mu g OVA was typically increased 1.4-fold. The increased amount o f reticulin showed no reduction after a 50-d period after the third allerge n challenge. A reduction in SEF was achieved by daily treatment with dexame thasone (DEX) for 8 d during the allergen challenge period, or by treatment with anti-interleukin-5 antibody (TRFK5) at the time of allergen challenge , Postchallenge treatment with DEX for 15 d resulted in significant resolut ion of previously established SEF, Severe nonallergic inflammation during r epeated exposure of airways to lipopolysaccharide did not induce SEF. The r esults indicate that development of SEF is associated with eosinophil infil tration into airways, and may occur only when the inflammatory stimulus is allergic in nature.