Goldblum S E, Yoneda K, Cohen D A, McClain C J
Department of Medicine, Veterans Administration Medical Center, Baltimore, Maryland 21201.
Infect Immun. 1988 Sep;56(9):2255-63. doi: 10.1128/iai.56.9.2255-2263.1988.
Interleukin-1 (IL-1) mediates components of the acute-phase response, stimulates granulocyte metabolism, and induces endothelial cell surface changes. We studied the effects of human recombinant IL-1 beta (rIL-1 beta) or rIL-1 alpha on circulating granulocytes, their sequestration within the pulmonary microvasculature, pulmonary edema formation, and changes in pulmonary vascular permeability to 125I-labeled albumin. rIL-1 beta administration induced significant (P less than 0.03) but transient granulocytopenia followed by significant (P less than 0.04) neutrophilia and significant (P less than 0.04) pulmonary leukostasis compared with saline-infused rabbits. Rabbits preinfused with 125I-labeled rabbit serum albumin and administered saline, rIL-1 beta, or rIL-1 alpha were sacrificed, and lung wet/dry weight ratios and bronchoalveolar lavage fluid and plasma 125I activities determined. Both rIL-1 beta and rIL-1 alpha increased lung wet/dry weight ratios (P less than 0.025 and P less than 0.01, respectively) compared with saline controls. rIL-1 beta increased bronchoalveolar lavage fluid/plasma 125I radioactivity ratios (P less than 0.025). Electron microscopic analysis of lung sections obtained from rIL-1 beta-infused animals demonstrated endothelial injury, perivascular edema, and extravasation of an ultrastructural permeability tracer. The observation that human rIL-1 can evoke acute pulmonary vascular endothelial injury and lung edema in rabbits supports the hypothesis that IL-1 may play a role in the pathogenesis of the adult respiratory distress syndrome.
白细胞介素-1（IL-1）介导急性期反应的组成部分，刺激粒细胞代谢，并诱导内皮细胞表面变化。我们研究了重组人IL-1β（rIL-1β）或rIL-1α对循环粒细胞的影响、它们在肺微血管系统中的滞留、肺水肿形成以及肺血管对125I标记白蛋白的通透性变化。与输注生理盐水的兔子相比，给予rIL-1β可导致显著（P<0.03）但短暂的粒细胞减少，随后是显著（P<0.04）的中性粒细胞增多和显著（P<0.04）的肺白细胞淤滞。对预先输注125I标记兔血清白蛋白并给予生理盐水、rIL-1β或rIL-1α的兔子进行处死，测定肺湿/干重比以及支气管肺泡灌洗液和血浆中的125I活性。与生理盐水对照组相比，rIL-1β和rIL-1α均增加了肺湿/干重比（分别为P<0.025和P<0.01）。rIL-1β增加了支气管肺泡灌洗液/血浆125I放射性比值（P<0.025）。对接受rIL-1β输注的动物的肺切片进行电子显微镜分析显示有内皮损伤、血管周围水肿以及超微结构通透性示踪剂的外渗。重组人IL-1可在兔子中引发急性肺血管内皮损伤和肺水肿这一观察结果支持了IL-1可能在成人呼吸窘迫综合征发病机制中起作用的假说。
