Prior SO2 exposure promotes airway inflammation and subepithelial fibrosis following repeated ovalbumin challenge.

Background Exposure to allergens or air pollutants often leads to asthma exacerbations associated with aggravation of airway inflammation. Although, repeated allergen challenge often induces chronic allergic airway inflammation (CAAI) and airway remodelling, yet, the effects of brief exposure to air pollutants such as SO₂ on development of CAAI and airway remodelling remain to be clarified. Objective The aim of the experiment was to investigate the effects of acute neutrophilic airway inflammation induced by brief exposure to SO₂ on development of CAAI and subepithelial fibrosis (SEF) in a murine model of asthma. Methods Acute airway inflammation was induced by brief exposure to 50 p.p.m. SO₂ (1 h/d, 3 days). CAAI and SEF in BALB/c mice were induced by repeated challenge with ovalbumin (OVA) for 5 or 9 weeks with or without prior exposure to SO₂. Bronchoalveolar lavage fluid (BALF) eosinophilia as index of CAAI, BALF endothelin-1 (ET-1) and TGF-β1 levels, morphometric evaluation of fibrotic area beneath subbasement membrane and lung hydroxyproline content (Hyp) as indexes of SEF were monitored. Results Exposure to SO₂ led to acute neutrophilic inflammation and epithelial sloughing with profound elevation of BALF ET-1. Repeated OVA challenge resulted in CAAI and SEF along with elevation of Hyp, increase of fibrotic area beneath subbasement membrane and elevation of BALF TGF-β1. Preceding SO₂ exposure exaggerated BALF eosinophilia, facilitated and enhanced SEF with more significant elevation of BALF ET-1 and TGF-β1 levels compared with OVA-challenged mice without prior exposure to SO₂. The increase of Hyp was positively correlated with elevation of BALF TGF-β1 during CAAI ( r=0.842, P<0.01). Conclusion This data demonstrated that SEF developed in parallel with severity and time course of CAAI following repeated OVA challenge. SO₂-induced acute epithelial injury and neutrophilic inflammation could enhance CAAI and promote SEF, probably through overexpression of ET-1 and TGF-β1. [ABSTRACT FROM AUTHOR]