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 alpha-chain (IL-4Ralpha) 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-4Ralpha -/- 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-4Ralpha.