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Differential Regulation by Glucocorticoid of Interleukin-13–induced Eosinophilia, Hyperresponsiveness, and Goblet Cell Hyperplasia in Mouse Airways

Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University; and First Department of Internal Medicine, Kurume University, Fukuoka, Japan

Correspondence and requests for reprints should be addressed to Hiromasa Inoue, M.D., Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: inoue{at}kokyu.med.kyushu-u.ac.jp

Interleukin (IL)-13 induces important features of bronchial asthma such as eosinophilic infiltration, airway hyperresponsiveness (AHR), and mucus hypersecretion. Although glucocorticoids suppress airway inflammation and remain the most effective therapy for asthma, the effects of glucocorticoids on the IL-13–dependent features are unknown. We studied the effects of dexamethasone on eotaxin production, eosinophil accumulation, goblet cell hyperplasia, and AHR after IL-13 administration into the airways of mice in vivo. MUC5AC gene expression, a marker of goblet cell hyperplasia, was also analyzed. IL-13 alone dose dependently induced AHR. Treatment with dexamethasone inhibited eotaxin expression and completely abolished eosinophil accumulation, but it did not affect AHR, MUC5AC overexpression, or goblet cell hyperplasia induced by IL-13. The effects of tumor necrosis factor- on IL-13–induced AHR were also examined. Tumor necrosis factor- did not affect AHR despite marked enhancement of eosinophil infiltration in IL-13–treated mice. These findings suggest that glucocorticoid is not sufficient to suppress IL-13–induced AHR or goblet cell hyperplasia and that eotaxin expression and eosinophilic inflammation do not have a causal relationship to the induction of AHR or goblet cell hyperplasia by IL-13. Control of steroid-resistant features induced by IL-13, including AHR and mucus production, may provide new therapeutic modalities for asthma.

Key Words: airway hyperreactivity • corticosteroid • cytokine • eosinophil • goblet cell metaplasia

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