Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model
Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model
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DOI：
10.1164/rccm.2105079
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发表时间：
2002-08-01
影响因子：
24.7
通讯作者：
Fukuda, T
中科院分区：
文献类型：
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作者：
Cheng, G;Arima, M;Fukuda, T
在动物和哮喘患者中进行的大量体外和体内研究表明，白细胞介素（IL）-9是哮喘中重要的炎症介质。为了检测IL-9拮抗作用对气道炎症的影响，在用雾化卵清蛋白激发前30分钟，静脉内给予卵清蛋白致敏的BALB/c小鼠抗IL-9抗体或同种型匹配的对照抗体。测定气道对乙酰甲胆碱的反应，并在末次抗原激发后24小时采集支气管肺泡灌洗液（BALF）样本。收获肺组织并进行组织病理学检查。卵白蛋白激发后，气道高反应性、肺内炎性细胞数和BALF中IL-4、IL-5和IL-13的产生显著增加。用抗IL-9抗体治疗显著预防了乙酰甲胆碱吸入引起的气道高反应性。IL-9阻断可减少BALF中嗜酸性粒细胞（0.3 +/- 0.1 x 10（5）和23.6 +/- 0.5 x 10（5）/ml，抗IL-9抗体/对照免疫球蛋白G）和淋巴细胞（0.2 +/- 0.2 x 10（5）和0.8 +/- 0.1 x 10（5）/ml）的数量。抗IL-9抗体处理还降低了BALF中IL-4（从70.6 +/- 4.6至30.8 +/- 5.2 pg/ml）、IL-5（从106.4 +/- 12至54.4 +/- 6.6 pg/ml）和IL-13（从44.2 +/- 7.6至30.1 +/- 5.5 pg/ml）的浓度。气道中巨噬细胞源性细胞因子的表达也通过IL-9阻断而降低。综上所述，我们的研究结果强调了IL-9在哮喘发病机制中的重要性，并提示阻断IL-9可能是支气管哮喘的一种新的治疗策略。
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 10(5) and 23.6 +/- 0.5 x 10(5)/ml, anti-IL-9 antibody/control immunoglobulin G) and lymphocytes (0.2 +/- 0.2 x 10(5) and 0.8 +/- 0.1 x 10(5)/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.