IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism
Date
2001
Authors
Pope, Samuel
Brandt, Eric
Mishra, Anil
Hogan, Simon
Zimmermann, Nives
Matthaei, Klaus
Foster, Paul S
Rothenberg, Marc E
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Mosby Inc
Abstract
Background: IL-13 induces several characteristic features of asthma, including airway eosinophilia, airway hyperresponsiveness, and mucus overproduction; however, the mechanisms involved are largely unknown. Objective: We hypothesized that IL-13 - induced inflammatory changes in the lung were dependent in part on IL-5 and eotaxin, two eosinophil-selective cytokines. Methods: Recombinant murine IL-13 was repeatedly administered to the lung by intranasal delivery until the characteristic features of asthma developed. To analyze the role of IL-5 and eotaxin, we subjected eotaxin gene-targeted, IL-5 gene-targeted, eotaxin/IL-5 - double-deficient, IL-5 transgenic, and wild-type mice of the Balb/C background to the experimental regime. Results: The induction of IL-13-mediated airway eosinophilia was found to occur independently of eosinophilia in the blood or bone marrow, indicating that IL-13-induced airway inflammation is primarily mediated by local effects of IL-13 in the lung. Eosinophil recruitment into both the lung tissue and bronchoalveolar lavage fluid was markedly attenuated in IL-5-deficient mice in comparison with wild-type controls. Accordingly, IL-13 delivery to IL-5 transgenic mice resulted in a large increase in airway eosinophils in comparison with wild-type mice. Interestingly, IL-13-induced eosinophilia in the bronchoalveolar lavage fluid of eotaxin-deficient mice was not impaired; however, these same mice failed to mount a significant tissue eosinophilia in response to IL-13. Finally, IL-13-induced mucus production was not affected by the presence of IL-5 or eotaxin, suggesting that IL-13-induced mucus secretion is mechanistically dissociated from airway eosinophilia. Conclusion: Selective components of the IL-13 - induced asthma phenotype - airway eosinophilia but not mucus secretion - are differentially regulated by IL-5 and eotaxin. IL-5 is required for IL-13 to induce eosinophilia throughout the lung, whereas eotaxin regulates the distribution of airway eosinophils.
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Keywords
Keywords: eotaxin; interleukin 13; interleukin 5; allergic disease; animal experiment; animal model; animal tissue; article; asthma; bone marrow; controlled study; eosinophilia; female; gene targeting; inflammation; lung lavage; male; mouse; mucus secretion; nonhum Allergy; Asthma; Chemokine; Eotaxin; Interleukin
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Source
Journal of Allergy and Clinical Immunology
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Journal article
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2037-12-31
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