Role of interleukin‐13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma

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Abstract
Background Interleukin‐13 is believed to be important in asthmatic inflammation and airway hyper‐reactivity. Objective To investigate the role of IL‐13 in chronic asthma, using an improved experimental model of asthma that reproduces most of the morphological features of the human disease. Methods BALB/c mice or gene‐targeted mice deficient in their ability to produce IL‐13 or the IL‐4 receptor α‐chain (IL‐4Rα) were sensitized to ovalbumin and exposed to aerosolized antigen for 30 min/day on 3 days/week for 6 weeks. Intraepithelial eosinophils, accumulation of chronic inflammatory cells in the airway wall, subepithelial fibrosis, epithelial hypertrophy and numbers of mucous cells were quantified histomorphometrically. Airway hyper‐reactivity (AHR) to a cholinergic agonist was assessed by barometric plethysmography. Results Compared with wild‐type animals, IL‐13 ‐/‐ mice exhibited diminished accumulation of eosinophils and chronic inflammatory cells, as well as reduced subepithelial fibrosis, epithelial hypertrophy and mucous cell hyperplasia (P < 0.01 for all comparisons). In contrast, AHR was still demonstrable in IL ‐13 ‐/‐ mice. In IL‐4Rα ‐/‐ mice the inflammatory response, subepithelial fibrosis and AHR were similar to wild‐type mice, although the receptor‐deficient mice had significantly less epithelial hypertrophy and mucous cell hyperplasia. Conclusion These results imply a critical role for IL‐13 in accumulation of intraepithelial eosinophils in chronic asthma, as well as in epithelial and subepithelial remodelling. In addition, they suggest that in chronic asthma, IL‐13 may be capable of signalling via a pathway that does not involve IL‐4Rα.