Fukuda T, Akutsu I, Numao T, Makino S
Department of Medicine and Clinical Immunology, Dokkyo University School of Medicine.
Arerugi. 1990 May;39(5):483-7.
We have previously demonstrated that Cyclosporin A (CyA), a T lymphocyte-selective immunosuppressive agent, reduced the delayed-phase bronchial eosinophil infiltration after antigen challenge in a guinea pig model of asthma. In the present study, we studied the effects of CyA on antigen-induced late asthmatic response (LAR) and bronchial hyperresponsiveness following LAR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hours before and 30 minutes before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine was significantly increased. However, when guinea pigs were treated with CyA from the beginning of immunization period, the development of LAR was completely inhibited, although similar magnitude of immediate bronchoconstriction was observed, and a subsequent increase in bronchial responsiveness was partially but significantly blocked. Since CyA has been shown to suppress activation of guinea pig T lymphocytes and their production of lymphokines, these results suggest that T cell factor(s) may be important for the elicitation of LAR and the antigen-induced bronchial hyperresponsiveness.
我们先前已经证明，环孢菌素A（CyA），一种T淋巴细胞选择性免疫抑制剂，在哮喘豚鼠模型中可减少抗原激发后的迟发性支气管嗜酸性粒细胞浸润。在本研究中，我们研究了CyA对抗原诱导的迟发性哮喘反应（LAR）以及LAR后支气管高反应性的影响。通过反复暴露于雾化卵清蛋白（OA）免疫的豚鼠，在抗原激发前24小时和30分钟静脉注射甲吡酮（一种皮质醇合成抑制剂），并且为防止因立即发生的严重支气管收缩而死亡，还注射了马来酸氯苯那敏。用高剂量OA进行抗原激发后，15只动物中有12只（80%）出现了LAR，并且对乙酰胆碱的支气管反应性显著增加。然而，当豚鼠从免疫期开始就用CyA治疗时，LAR的发展被完全抑制，尽管观察到了相似程度的即刻支气管收缩，并且随后支气管反应性的增加被部分但显著地阻断。由于已经证明CyA可抑制豚鼠T淋巴细胞的激活及其细胞因子的产生，这些结果表明T细胞因子可能对LAR的引发以及抗原诱导的支气管高反应性很重要。
