Hessel E M, Van Oosterhout A J, Van Ark I, Van Esch B, Hofman G, Van Loveren H, Savelkoul H F, Nijkamp F P
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, the Netherlands.
Am J Respir Cell Mol Biol. 1997 Mar;16(3):325-34. doi: 10.1165/ajrcmb.16.3.9070618.
In this study the role of interleukin (IL)4, IL5, interferon (IFN) gamma, and tumor necrosis factor (TNF) alpha in the development of airway hyperresponsiveness and inflammatory cell infiltration was investigated using a murine model for allergic asthma. Mice were sensitized with ovalbumin and subsequently challenged repeatedly with ovalbumin aerosols. During the challenge period, mice were treated with monoclonal antibodies directed against IL4, IL5, IFN gamma, or TNF alpha. Control antibody-treated mice showed airway hyperresponsiveness to methacholine and the presence of eosinophils in bronchoalveolar lavage (BAL). Treatment with antibodies to IFN gamma completely abolished development of airway hyperresponsiveness in ovalbumin-challenged animals. After treatment with antibodies to TNF alpha, airway hyperresponsiveness in the ovalbumin-challenged animals was partially but not significantly inhibited. Antibodies to IL4 or IL5 did not inhibit airway hyperresponsiveness. The presence of eosinophils in BAL of ovalbumin-challenged mice was completely inhibited after treatment with antibodies to IL5. Treatment with antibodies to IL4, IFN gamma, or TNF alpha had no effect on eosinophilia. Because IFN gamma and IL5 have either an effect on the induction of airway hyperresponsiveness or on the development of eosinophil infiltration, our results suggest that the two phenomena are differentially regulated.
在本研究中，使用过敏性哮喘小鼠模型，研究了白细胞介素（IL）-4、IL-5、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α在气道高反应性发展和炎性细胞浸润中的作用。用卵清蛋白使小鼠致敏，随后反复用卵清蛋白气雾剂进行激发。在激发期间，用针对IL-4、IL-5、IFN-γ或TNF-α的单克隆抗体治疗小鼠。用对照抗体治疗的小鼠显示出对乙酰甲胆碱的气道高反应性以及支气管肺泡灌洗（BAL）中嗜酸性粒细胞的存在。用IFN-γ抗体治疗完全消除了卵清蛋白激发动物气道高反应性的发展。用TNF-α抗体治疗后，卵清蛋白激发动物的气道高反应性受到部分但不显著的抑制。IL-4或IL-5抗体未抑制气道高反应性。用IL-5抗体治疗后，卵清蛋白激发小鼠BAL中嗜酸性粒细胞的存在被完全抑制。用IL-4、IFN-γ或TNF-α抗体治疗对嗜酸性粒细胞增多无影响。由于IFN-γ和IL-5对气道高反应性的诱导或嗜酸性粒细胞浸润的发展有影响，我们的结果表明这两种现象受到不同的调节。
