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, Marc E. Rothenberg, Samuel M. Pope, Simon P. Hogan, Klaus I. Matthaei, Paul S. Foster

    Research output: Contribution to journalArticlepeer-review

    272 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)594-601
    Number of pages8
    JournalJournal of Allergy and Clinical Immunology
    Volume108
    Issue number4
    DOIs
    Publication statusPublished - 2001

    Fingerprint

    Dive into the research topics of 'IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism'. Together they form a unique fingerprint.

    Cite this