Dorsch W, Frey L, Müller W
Naunyn Schmiedebergs Arch Pharmacol. 1984 Mar;325(3):275-82. doi: 10.1007/BF00495955.
The term "allergen tachyphylaxis" (AT) describes a progressively decreased bronchial reactivity to allergen exposition after repeated allergen challenge [in our test system measured by sequential inhalative antigen challenge of sensitized guinea pigs (GP)]. The hypothesis that AT is mediated by endogenous prostaglandin E (PGE) biosynthesis was tested in vivo on GP sensitized to ovalbumin (OA). Different groups of animals were challenged with simultaneous inhalation of OA (repeatedly at time 0, 10, 20, 60 and 70 min) together with inhibitors of PGE-biosynthesis ( parachloromercurobenzoic acid = PCMB, copper sulfate = Cu, copper dithiotreitol complex = CuDTT , dithiotreitol = DTT and dimercaptopropanol = DMP) or agents increasing PGE production (aurothioglucose = Au, zinc dithiotreitol complex = ZnDTT and reduced glutathion = GSH). Bronchial obstruction was measured by whole body plethysmography . PCMB, Cu, CuDTT , DTT and DMP inhibited AT, whereas Au and ZnDTT enhanced AT. Acetylsalicylic acid (ASA) treatment prevented AT. Aerosols of PGE2, but not of prostacyclin or prostaglandin D2 restored AT in ASA treated animals. In addition to these in vivo experiments in vitro investigations showed that PCMB, Cu and DTT decreased while ZnDTT increased PGE biosynthesis of allergen challenged GP lungs. It is concluded that AT, an important self-protecting mechanism of GP bronchial asthma, is mediated at least in part via endogenous PGE.
术语“变应原速发耐受”（AT）描述的是在反复进行变应原激发后（在我们的测试系统中，通过对致敏豚鼠进行连续吸入抗原激发来测量），支气管对变应原暴露的反应性逐渐降低。关于AT由内源性前列腺素E（PGE）生物合成介导的假说，在对卵清蛋白（OA）致敏的豚鼠体内进行了验证。不同组的动物在吸入OA（分别在0、10、20、60和70分钟重复吸入）的同时，还吸入PGE生物合成抑制剂（对氯汞苯甲酸 = PCMB、硫酸铜 = Cu、铜二硫苏糖醇络合物 = CuDTT、二硫苏糖醇 = DTT和二巯丙醇 = DMP）或增加PGE生成的药物（金硫葡糖 = Au、锌二硫苏糖醇络合物 = ZnDTT和还原型谷胱甘肽 = GSH）。通过全身体积描记法测量支气管阻塞情况。PCMB、Cu、CuDTT、DTT和DMP抑制了AT，而Au和ZnDTT增强了AT。乙酰水杨酸（ASA）治疗可预防AT。PGE2气雾剂，但前列环素或前列腺素D2气雾剂不能恢复ASA治疗动物的AT。除了这些体内实验外，体外研究还表明，PCMB、Cu和DTT可降低，而ZnDTT可增加变应原激发的豚鼠肺组织中PGE的生物合成。结论是，AT作为豚鼠支气管哮喘的一种重要自我保护机制，至少部分是通过内源性PGE介导的。
