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

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 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)