Lucht W D, Bernard G R, Butka B, Brigham K L
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
Am J Med Sci. 1988 Aug;296(2):98-102. doi: 10.1097/00000441-198808000-00004.
The Adult Respiratory Distress Syndrome (ARDS) most frequently is the result of sepsis. Accumulation of neutrophils in lung interstitium is a well-documented phenomenon, but the nature of their presence remains obscure. We hypothesized that endotoxin causes the release of substances into lung lymph that activate neutrophils and that methylprednisolone may prevent sequestration and activation of neutrophils. We used the sheep lung lymph fistula-endotoxin model of ARDS to test this hypothesis. Unanesthetized animals were given either 0.5 microgram/kg of E. coli endotoxin intravenously alone or, on a different experimental day, an identical dose of endotoxin preceded by a 1 gm bolus of methylprednisolone plus a 1 gm/hr continuous infusion. Endotoxin infusion caused the release of substances into lung lymph that were capable of stimulating normal sheep neutrophils to aggregate, migrate, and release superoxide. This activity appeared within 1 hour of endotoxin and persisted for at least 4 hours. Pretreatment by methylprednisolone did not prevent the early activity but did significantly reduce such activity 3-4 hours after endotoxin, when the permeability defects caused by endotoxin are most pronounced. We speculate that endotoxin-stimulated production of humoral neutrophil-activating substances in the lung may play a role in the pathogenesis of acute lung injury.
成人呼吸窘迫综合征（ARDS）最常见的病因是败血症。中性粒细胞在肺间质中的聚集是一个有充分文献记载的现象，但其存在的本质仍不清楚。我们推测内毒素会导致物质释放到肺淋巴液中，从而激活中性粒细胞，而甲基强的松龙可能会阻止中性粒细胞的滞留和激活。我们使用ARDS的绵羊肺淋巴瘘-内毒素模型来验证这一假设。未麻醉的动物要么单独静脉注射0.5微克/千克的大肠杆菌内毒素，要么在不同的实验日，先静脉注射1克甲基强的松龙推注剂量，再以1克/小时的速度持续输注，然后注射相同剂量的内毒素。内毒素输注导致物质释放到肺淋巴液中，这些物质能够刺激正常绵羊中性粒细胞聚集、迁移并释放超氧化物。这种活性在内毒素注射后1小时内出现，并持续至少4小时。甲基强的松龙预处理并不能阻止早期活性，但在内毒素注射后3 - 4小时，当内毒素引起的通透性缺陷最为明显时，能显著降低这种活性。我们推测内毒素刺激肺中产生的体液性中性粒细胞激活物质可能在急性肺损伤的发病机制中起作用。
