Role of Th2 responses in the development of allergen‐induced airway remodelling in a murine model of allergic asthma

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Abstract
To clarify the involvement of Th2 responses in the development of allergen‐induced airway remodelling, we investigated the effect of anti‐CD4 monoclonal antibody (mAb) and anti‐CD8 mAb, and the responses of IL‐4 gene‐knockout (KO) mice in a murine model of allergic asthma. Mice were immunized twice by intraperitoneal injections of ovalbumin (OA), and exposed to aeroallergen (OA, 1% w v−1) for 3 weeks. Twenty‐four hours after the final challenge, airway responsiveness to acetylcholine was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out. Anti‐CD4 mAb (1 mg kg−1) clearly inhibited allergen‐induced increases in airway responsiveness to acetylcholine, the number of eosinophils in BAL fluid, serum OA‐specific IgE levels, IL‐13 and transforming growth factor‐β1 levels in BAL fluid, and amount of hydroxyproline in the lung by 100, 99, 100, 100, 84, and 60%, respectively. Furthermore, the antibody (1 mg kg−1) also attenuated allergen‐induced goblet cell hyperplasia in the epithelium and subepithelial fibrosis by 72 and 83%, respectively. In contrast, anti‐CD8 mAb (1 mg kg−1) showed no effect on each parameter. Furthermore, all these parameters were attenuated in IL‐4KO mice by 57, 93, 100, 45, 84 and 60%, and also 72 and 83%, respectively. These findings suggest that Th2 responses play a critical role for the development of allergen‐induced airway remodelling, and that the inhibition of Th2 responses, e.g. using anti‐CD4 mAb, is a therapeutic approach for the treatment of airway remodelling in asthma. British Journal of Pharmacology (2003) 138, 912–920. doi:10.1038/sj.bjp.0705105