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

Roy C Levitt, M. R McLane, D. MacDonald, V. Ferrante, C. Weiss, T. Zhou, K. J. Holroyd, N. C. Nicolaides

Research output: Contribution to journalArticle

96 Citations (Scopus)

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
JournalJournal of Allergy and Clinical Immunology
Volume103
Issue number5 II
StatePublished - Jul 6 1999
Externally publishedYes

Fingerprint

Interleukin-9
Asthma
Immunoglobulin E
Therapeutics
Eosinophilia
Eosinophils
Lung
Serum
Therapeutic Human Experimentation
Inflammation
Bronchoalveolar Lavage
Developed Countries

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Levitt, R. C., R McLane, M., MacDonald, D., Ferrante, V., Weiss, C., Zhou, T., ... Nicolaides, N. C. (1999). IL-9 pathway in asthma: New therapeutic targets for allergic inflammatory disorders. Journal of Allergy and Clinical Immunology, 103(5 II).

IL-9 pathway in asthma : New therapeutic targets for allergic inflammatory disorders. / Levitt, Roy C; R McLane, M.; MacDonald, D.; Ferrante, V.; Weiss, C.; Zhou, T.; Holroyd, K. J.; Nicolaides, N. C.

In: Journal of Allergy and Clinical Immunology, Vol. 103, No. 5 II, 06.07.1999.

Research output: Contribution to journalArticle

Levitt, RC, R McLane, M, MacDonald, D, Ferrante, V, Weiss, C, Zhou, T, Holroyd, KJ & Nicolaides, NC 1999, 'IL-9 pathway in asthma: New therapeutic targets for allergic inflammatory disorders', Journal of Allergy and Clinical Immunology, vol. 103, no. 5 II.
Levitt, Roy C ; R McLane, M. ; MacDonald, D. ; Ferrante, V. ; Weiss, C. ; Zhou, T. ; Holroyd, K. J. ; Nicolaides, N. C. / IL-9 pathway in asthma : New therapeutic targets for allergic inflammatory disorders. In: Journal of Allergy and Clinical Immunology. 1999 ; Vol. 103, No. 5 II.
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