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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-6-8
pubmed:abstractText
To study pathogenetic mechanisms in chronic asthma, we employed a novel experimental model that replicates characteristic features of the human disease. Chronic inflammation and epithelial changes, specifically localized to the airways, were induced by repeated exposure of systemically sensitized BALB/c mice to low mass concentrations of aerosolized ovalbumin for 6 weeks. The contribution of Th2 cytokine-driven inflammation to the development of airway lesions and hyperreactivity was assessed in cytokine-deficient mice. In interleukin-5-deficient animals, intraepithelial eosinophils and chronic inflammatory cells in the lamina propria of the airways were markedly decreased; however, these animals developed epithelial hypertrophy and subepithelial fibrosis comparable with that observed in sensitized wild type mice. Airway hyperreactivity to inhaled methacholine did not develop in interleukin-5-deficient mice. In contrast, interleukin-4-deficient mice exhibited no decrease in airway inflammation, but had significantly greater epithelial hypertrophy and subepithelial fibrosis, as well as exaggerated hyperreactivity to methacholine. We conclude that interleukin-5, but not interleukin-4, plays a central role in the development of chronic inflammation of the airways and the induction of airway hyperreactivity. Furthermore, chronic epithelial and fibrotic changes occur independently of interleukin-5 and are not required for the development of airway hyperreactivity. The dissociation between airway wall remodeling and airway hyperreactivity has important implications for therapeutic approaches to chronic asthma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
655-62
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Dissociation of inflammatory and epithelial responses in a murine model of chronic asthma.
pubmed:affiliation
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra. Paul.Foster@anu.edu.au
pubmed:publicationType
Journal Article