Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice
Effect of anti-mIL-9 antibody on the development of pulmonary inflammation and airway hyperresponsiveness in allergic mice
复制标题
DOI：
10.1165/ajrcmb.25.5.4533
复制
发表时间：
2001-11-01
影响因子：
6.4
通讯作者：
Chapman, RW
中科院分区：
文献类型：
--
作者：
Kung, TT;Luo, B;Chapman, RW
白介素9是一种T细胞来源的细胞因子，对辅助性T细胞、B细胞和肥大细胞具有多效性。因此，IL-9可能在变态反应性肺炎性疾病的发生发展中起重要作用。在这项研究中，抗小鼠IL-9(抗mIL-9)抗体(Ab)对致敏和卵清蛋白(OVA)致敏和激发的小鼠肺嗜酸性粒细胞增多症、肺组织病理改变、血清免疫球蛋白(Ig)E水平和对乙酰甲胆碱的高反应性(AHR)进行了评价。此外，还检测了肺组织中IL-4、IL-5、IL-13和干扰素-γ信使RNA(MRNA)的稳态水平。抗mIL-9抗体200µg/只，在致敏过程中分4次给药，或在卵清蛋白攻击前单次给药。OVA致敏小鼠表现出明显的肺嗜酸性粒细胞增多、上皮损伤和杯状细胞增生。OVA激发后，肺组织中IL-4、IL-5和IL-13的mRNA水平也升高。在致敏的、受到挑战的小鼠中，AHR也增加了两倍。用4种剂量的抗mIL-9单抗处理致敏和攻击小鼠，可显著降低肺嗜酸粒细胞增多、血清IgE水平、杯状细胞增生、气道上皮损伤和AHR，但对肺组织IL-4、IL-5和IL-13mRNA水平无明显影响。单剂抗体在所有测量中都无效。这些结果表明，mIL-9抗体可抑制小鼠过敏性肺部炎症和AHR的发展。
Interleukin (IL)-9 is a T-cell-derived cytokine with pleiotropic activities on T helper 2 cells, B cells, and mast cells. IL-9 may therefore play an important role in the development of allergic pulmonary inflammatory diseases. In this study, an anti-mouse IL-9 (anti-mIL-9) antibody (Ab) was evaluated against pulmonary eosinophilia, histopathologic changes in lung tissues, serum immunoglobulin (Ig) E levels, and airway hyperresponsiveness (AHR) to methacholine in mice sensitized and challenged with ovalbumin (OVA). Additionally, steady-state levels of IL-4, IL-5, IL-13, and interferon-gamma messenger RNA (mRNA) in the lungs were measured. The anti-mIL-9 Ab (200 mug/mouse, intraperitoneally) was given as either four doses during the sensitization period or as a single dose before OVA challenge. Sensitized mice challenged with OVA displayed marked pulmonary eosinophilia, epithelial damage, and goblet cell hyperplasia. OVA challenge also increased mRNA levels of IL-4, IL-5, and IL-13 in the lungs. AHR was also increased twofold in sensitized, challenged mice. Treatment of sensitized, challenged mice with four doses of anti-mIL-9 Ab significantly reduced pulmonary eosinophilia, serum IgE levels, goblet cell hyperplasia, airway epithelial damage, and AHR, but had no effect on IL-4, IL-5, and IL-13 mRNA levels in the lungs. A single dose of the antibody was ineffective on all measures. These results indicate that an antibody to mIL-9 inhibits the development of allergic pulmonary inflammation and AHR in mice.