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
Citations
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IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism.
Samuel M. Pope,Eric B. Brandt,Anil Mishra,Simon P. Hogan,Nives Zimmermann,Klaus I. Matthaei,Paul S. Foster,Marc E. Rothenberg +7 more
TL;DR: Selective components of the IL-13-induced asthma phenotype--airway eosinophilia but not mucus secretion--are differentially regulated by IL-5 and eotaxin.
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Modulation of Airway Inflammation by Passive Transfer of Allergen-Specific Th1 and Th2 Cells in a Mouse Model of Asthma
David A. Randolph,Cynthia J. L. Carruthers,Susanne J. Szabo,Kenneth M. Murphy,David D. Chaplin +4 more
TL;DR: It is shown that in the murine model of OVA-induced airway inflammation, both Th1 and Th2 cells are recruited to the airways and Ag-specific Th1 cells are not protective in this model of asthma, but rather may potentiate the inflammatory response.
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A Novel T Cell-Regulated Mechanism Modulating Allergen-Induced Airways Hyperreactivity in BALB/c Mice Independently of IL-4 and IL-5
Simon P. Hogan,Klaus I. Matthaei,Janine M. Young,Aulikki Koskinen,Ian G. Young,Paul S. Foster +5 more
TL;DR: This investigation demonstrates the existence in BALB/c mice of a novel CD4+ T cell pathway for modulating airways hyperreactivity, which may provide an explanation for the dissociation of airways eosinophilia from the development of airwayhyperreactivity observed in some cases of asthma and in animal models of this disease.
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IL-33 Exacerbates Eosinophil-Mediated Airway Inflammation
TL;DR: It is demonstrated that the IL-33/ST2 signaling pathway activates airway eosinophils that exacerbate airway inflammation in an autocrine and paracrine manner.
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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.