| Blocking induction of T helper type 2 responses prevents development of disease in a model of childhood asthma. | |
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MedLine Citation:
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PMID: 21501148 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Early-life respiratory viral infections are linked to subsequent development of allergic asthma in children. We assessed the underlying immunological mechanisms in a novel model of the induction phase of childhood asthma. BALB/c mice were infected neonatally with pneumonia virus of mice, then sensitized intranasally with ovalbumin following recovery. Animals were challenged with low levels of aerosolized ovalbumin for 4 weeks to induce changes of chronic asthma, then received a single moderate-level challenge to elicit mild acute allergic inflammation. To inhibit the initial induction of a T helper type 2 (Th2) response, we administered neutralizing antibodies against interleukin (IL)-4 or IL-25, then assessed development of airway inflammation and remodelling. Anti-IL-4 administered during chronic challenge prevented development of chronic and acute allergic inflammation, as well as goblet cell hyperplasia/metaplasia, but features of remodelling such as subepithelial fibrosis and epithelial hypertrophy were unaffected. In contrast, anti-IL-25 had limited effects on the airway inflammatory response but prevented key changes of remodelling, although it had no effect on goblet cells. Both antibodies suppressed development of a Th2 response, while anti-IL-25 also promoted a Th17 response. In further experiments, anti-IL-25 was administered in early life alone, and again had limited effects on airway inflammation, but prevented development of airway wall remodelling. We conclude that in this murine model of childhood asthma, administration of anti-IL-4 or anti-IL-25 prevents development of some key features of asthma, suggesting that suppression of development of a Th2 response during the neonatal period or later in childhood could be effective for primary prevention. |
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Authors:
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J S Siegle; N Hansbro; C Dong; P Angkasekwinai; P S Foster; R K Kumar |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-19 |
Journal Detail:
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Title: Clinical and experimental immunology Volume: - ISSN: 1365-2249 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. |
Affiliation:
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Inflammation and Infection Research Centre, University of New South Wales, Sydney Centre for Asthma and Respiratory Disease, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia Department of Immunology, University of Texas, Houston, TX, USA Department of Medical Technology, Thammasat University, Pathumthani, Thailand. |
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