Abstract | BACKGROUND: 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.
|
Authors | R K Kumar, C Herbert, M Yang, A M L Koskinen, A N J McKenzie, P S Foster |
Journal | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
(Clin Exp Allergy)
Vol. 32
Issue 7
Pg. 1104-11
(Jul 2002)
ISSN: 0954-7894 [Print] England |
PMID | 12100061
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Interleukin-13
- Receptors, Interleukin-4
|
Topics |
- Animals
- Asthma
(pathology)
- Bronchial Hyperreactivity
(etiology)
- Chronic Disease
- Disease Models, Animal
- Eosinophils
(physiology)
- Epithelium
(pathology)
- Female
- Fibrosis
- Interleukin-13
(physiology)
- Mice
- Mice, Inbred BALB C
- Receptors, Interleukin-4
(physiology)
- Trachea
(pathology)
|