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 language | English (US) |
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Pages (from-to) | 410-419 |
Number of pages | 10 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 118 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2006 |
Externally published | Yes |
Keywords
- Airways hyperresponsiveness
- IL-13
- IL-4
- IL-4 receptor
- eosinophil
- goblet cell
- mouse
- mucus
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology