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


CONCLUSIONS
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.
Kumar
R K
RK
Inflammation Research Unit, Department of Pathology, University of New South Wales, Sydney, Australia. R.Kumar@unsw.edu.au
Herbert
C
C
Yang
M
M
Koskinen
A M L
AM
McKenzie
A N J
AN
Foster
P S
PS
D000818:Animals; D001249:Asthma / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004804:Eosinophils / Q000502:physiology*; D004848:Epithelium / Q000473:pathology; D005260:Female; D005355:Fibrosis; D018793:Interleukin-13 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019948:Receptors, Interleukin-4 / Q000502:physiology; D014132:Trachea / Q000473:pathology*
D018793:Interleukin-13; D019948:Receptors, Interleukin-4