IL-9 pathway in asthma: New therapeutic targets for allergic inflammatory disorders

Roy Clifford Levitt, Michael R. McLane, Dorothy MacDonald, Veronica Ferrante, Christine Weiss, Tingyi Zhou, Kenneth James Holroyd, Nicholas C. Nicolaides

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Background: Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of allergic inflammation and bronchial hyperresponsiveness (BHR). The incidence of asthma continues to rise in industrialized countries despite advances in the identification of cellular and molecular mediators that are associated with the disease. Because of its importance in human health, additional research and alternative therapeutic strategies are justified to create more effective treatments for this debilitating disease. Objective: Studies use recombinant inbred mice to demonstrate that BHR in mouse models of asthma is associated with a genetic alteration at the IL-9 locus, where IL-9 expression in lung is strongly associated with bronchial responsiveness. We have investigated the ability of intratracheal instilled IL-9 to induce asthmatic-like responses in naive C57BL/6 (B6) mice, which express very low levels of IL-9. Methods: IL-9 or vehicle was intratracheal instilled in naive B6 mice for 10 days. Mice were analyzed for effects on BHR, lung eosinophilia, and serum total IgE levels. Results: Phenotypic effects of B6 mice instilled with IL-9 were increased eosinophils in the bronchoalveolar lavage and significantly elevated serum total IgE. Moreover, IL-9 was found to induce IL-5Rα in vivo and in vitro, suggesting a potential mechanism for the novel actions described for IL-9 on eosinophils. Conclusion: Increased levels of IL-9 in the airway of naive B6 mice induced lung eosinophilia and serum total IgE levels, which are 2 clinical features of asthma. These data support a central role for the IL-9 pathway in the complex pathogenesis of allergic inflammation.

Original languageEnglish (US)
Pages (from-to)S485-S491
JournalJournal of Allergy and Clinical Immunology
Volume103
Issue number5 SUPPL.
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Keywords

  • Allergy
  • Asthma
  • Eosinophils
  • IgE
  • IL-9
  • Mouse models

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'IL-9 pathway in asthma: New therapeutic targets for allergic inflammatory disorders'. Together they form a unique fingerprint.

  • Cite this

    Levitt, R. C., McLane, M. R., MacDonald, D., Ferrante, V., Weiss, C., Zhou, T., Holroyd, K. J., & Nicolaides, N. C. (1999). IL-9 pathway in asthma: New therapeutic targets for allergic inflammatory disorders. Journal of Allergy and Clinical Immunology, 103(5 SUPPL.), S485-S491. https://doi.org/10.1016/S0091-6749(99)70165-X