Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.
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TLDR
Results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.Abstract:
Airways inflammation is thought to play a central role in the pathogenesis of asthma. However, the precise role that individual inflammatory cells and mediators play in the development of airways hyperreactivity and the morphological changes of the lung during allergic pulmonary inflammation is unknown. In this investigation we have used a mouse model of allergic pulmonary inflammation and interleukin (IL) 5-deficient mice to establish the essential role of this cytokine and eosinophils in the initiation of aeroallergen-induced lung damage and the development of airways hyperreactivity. Sensitization and aerosol challenge of mice with ovalbumin results in airways eosinophilia and extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged mice also display airways hyperreactivity to beta-methacholine. In IL-5-deficient mice, the eosinophilia, lung damage, and airways hyperreactivity normally resulting from aeroallergen challenge were abolished. Reconstitution of IL-5 production with recombinant vaccinia viruses engineered to express this factor completely restored aeroallergen-induced eosinophilia and airways dysfunction. These results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.read more
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References
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Journal ArticleDOI
Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma
Douglas S. Robinson,Qutayba Hamid,Sun Ying,Anne Tsicopoulos,J. Barkans,Andrew Bentley,Christopher Corrigan,Stephen R. Durham,A. B. Kay +8 more
TL;DR: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
Journal ArticleDOI
Cellular events in the bronchi in mild asthma and after bronchial provocation.
TL;DR: It is concluded that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.
Journal ArticleDOI
Macrophages and polymorphonuclear neutrophils in lung defense and injury
Yves Sibille,Herbert Y. Reynolds +1 more
TL;DR: Alveolar macrophages are part of the regulatory mechanisms of PMN mobility and adherence that appears to be crucial in the initiation of some inflammatory reactions, and this supports a central role for alveolarmacrophages in the regulation of PMn traffic in the lungs.
Journal ArticleDOI
Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions.
TL;DR: Bronchoalveolar lavage was performed in 19 asthmatic patients and in 5 control subjects to suggest that eosinophils and their mediators might be involved in the development of LAR after allergen inhalation.
Journal ArticleDOI
Recombinant human interleukin 5 is a selective activator of human eosinophil function.
Angel F. Lopez,Colin J. Sanderson,Jennifer R. Gamble,Hugh Campbell,Ian G. Young,Mathew A. Vadas +5 more
TL;DR: Human rIL-5 was found to selectively stimulate morphological changes and the function of human eosinophils, and is thus a prime candidate for the selective eOSinophilia and eos inophil activation seen in disease.