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Anti–Interleukin-9 Antibody Treatment Inhibits Airway Inflammation and Hyperreactivity in Mouse Asthma Model

Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi, Japan

Correspondence and requests for reprints should be addressed to Takeshi Fukuda, M.D., Ph.D., Departments of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Mibu-machi, Shimotsuga-gun, Tochigi, 321–0293, Japan. E-mail: cheng{at}dokkyomed.ac.jp

Numerous in vitro and in vivo studies in both animals and patients with asthma have shown that interleukin (IL)-9 is an important inflammatory mediator in asthma. To examine the effects of IL-9 antagonism on airway inflammation, ovalbumin-sensitized BALB/c mice were intravenously given anti–IL-9 antibody or an isotype-matched control antibody 30 minutes before challenge with aerosolized ovalbumin. Airway response to methacholine was measured, and samples of bronchoalveolar lavage fluid (BALF) were obtained 24 hours after the last antigen challenge. Lung tissue was harvested and examined histopathologically. After ovalbumin challenge, there were significant increases in airway hyperreactivity, the numbers of inflammatory cells in lung, and IL-4, IL-5, and IL-13 production in BALF. Treatment with anti–IL-9 antibody significantly prevented airway hyperreactivity in response to methacholine inhalation. Blockade of IL-9 reduced the numbers of eosinophils (0.3 ± 0.1 x 10⁵ and 23.6 ± 0.5 x 10⁵/ml, anti–IL-9 antibody/control immunoglobulin G) and lymphocytes (0.2 ± 0.2 x 10⁵ and 0.8 ± 0.1 x 10⁵/ml) in BALF. Anti–IL-9 antibody treatment also reduced the concentrations of IL-4 (from 70.6 ± 4.6 to 30.8 ± 5.2 pg/ml), IL-5 (from 106.4 ± 12 to 54.4 ± 6.6 pg/ml), and IL-13 (from 44.2 ± 7.6 to 30.1 ± 5.5 pg/ml) in BALF. Macrophage-derived cytokine expression in the airways was also decreased by IL-9 blockade. Taken together, our findings emphasize the importance of IL-9 in the pathogenesis of asthma and suggest that blockade of IL-9 may be a new therapeutic strategy for bronchial asthma.

Key Words: interleukin-9 • eosinophils • asthma • airway hyperreactivity • mouse

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