Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.
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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
Citations
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Requirement for IL-13 Independently of IL-4 in Experimental Asthma
Gabriele Grünig,Martha L. Warnock,Adil E. Wakil,Rajeev Venkayya,Frank Brombacher,Donna M. Rennick,Dean Sheppard,Markus Mohrs,Debra D. Donaldson,Richard M. Locksley,David B. Corry +10 more
TL;DR: This article showed that IL-4 receptor α chain-dependent pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL4 receptor and showed that selective neutralization of IL-13, a cytokine related to interleukin-4 that also binds to the α chain of the IL 4 receptor, ameliorated asthma phenotype.
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Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response
Margaret J Leckie,Anneke ten Brinke,Jamey Khan,Zuzana Diamant,Brian J. O'Connor,Christine M Walls,A. Mathur,Hugh C Cowley,K. Fan Chung,Ratko Djukanovic,Trevor T. Hansel,Stephen T. Holgate,Peter J. Sterk,Peter J. Barnes +13 more
TL;DR: A single dose of monoclonal antibody to IL-5 decreased blood eosinophils for up to 16 weeks and sputum eosInophils at 4 weeks, which has considerable therapeutic potential for asthma and allergy, however, the findings question the role of eos inophils in mediating the late asthmatic response and causing airway hyper-responsiveness.
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Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production
Zhou Zhu,Robert J. Homer,Robert J. Homer,Zhonde Wang,Qingsheng Chen,Gregory P. Geba,Gregory P. Geba,Jingming Wang,Yong Zhang,Jack A. Elias +9 more
TL;DR: The targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR in transgene-positive animals.
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Noninvasive Measurement of Airway Responsiveness in Allergic Mice Using Barometric Plethysmography
Eckard Hamelmann,Jürgen Schwarze,Katsuyuki Takeda,A. Oshiba,Gary L. Larsen,Charles G. Irvin,Erwin W. Gelfand +6 more
TL;DR: Measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice, and it is shown that AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration.
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Immunologic basis of antigen-induced airway hyperresponsiveness
TL;DR: Current understanding of the pathophysiologic mechanisms by which Th2 cytokines induce airway disease, and the factors that predispose to the generation of these pathogenic cells in response to inhalation of ubiquitous aero-allergens are discussed.
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