IL-4 induces IL-13-independent allergic airway inflammation

Charles Perkins, Marsha Wills-Karp, Fred D. Finkelman

Research output: Contribution to journalArticle

Abstract

Background: The related T H2 cytokines IL-4 and IL-13 are produced during allergic responses, signal through receptors that contain IL-4 receptor (IL-4R) α, and promote allergic inflammation by activating signal transducer and activator of transcription 6. IL-4 promotes T H2 response induction, and IL-13 is necessary and sufficient to induce airways hyperresponsiveness (AHR) and goblet cell hyperplasia in some mouse models of asthma. The nonredundant role of IL-13 could reflect unique IL-13 activation of a signaling pathway, inhibitory effects induced by IL-4 but not IL-13, or greater production-potency of IL-13 than IL-4. Objectives: We sought to distinguish among these possibilities by determining whether IL-4 inhalation can induce acute allergic airways disease in the absence of IL-13. Methods: Mice were inoculated intratracheally with IL-13 or a long-acting formulation of IL-4. Responses of IL-13-deficient and IL-13-sufficient mice were compared, as were responses in mice treated with a potent IL-13 antagonist, anti-IL-4Rα antibody, or control reagents. Results: IL-4 inhalation stimulated bronchoalveolar lavage fluid eosinophilia, AHR, and goblet cell hyperplasia. These responses were similar in IL-13-deficient and IL-13-sufficient mice and were not inhibited by an IL-13 antagonist but were blocked by anti-IL-4Rα antibody. Conclusion: IL-4 can induce IL-13-independent AHR and goblet cell hyperplasia. Thus the greater role for IL-13 than IL-4 in the induction of these acute allergy-related changes reflects increased production, potency, or both of IL-13 relative to IL-4 rather than a unique IL-13-signaling pathway or a suppressive effect of IL-4. Clinical implications: Dual IL-4/IL-13 inhibition might be more effective than selective IL-13 inhibition at suppressing allergic inflammation in some circumstances.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume118
Issue number2
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Keywords

  • Airways hyperresponsiveness
  • IL-13
  • IL-4
  • IL-4 receptor
  • eosinophil
  • goblet cell
  • mouse
  • mucus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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