Redl H, Schlag G, Schiesser A, Davies J
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
J Infect Dis. 1995 Jun;171(6):1522-7. doi: 10.1093/infdis/171.6.1522.
This study was designed to test whether thrombomodulin is shed in septic baboons and whether shedding is blocked by antibody to tumor necrosis factor (anti-TNF). Live Escherichia coli were injected intravenously into 24 baboons according to one of the following regimens: 5 x 10(8) or 2 x 10(9) cfu/kg (n = 6/8), 2 x 10(9) cfu/kg with placebo (n = 5), or pretreatment with 1 mg/kg anti-TNF 2 h before E. coli injection (n = 5). E. coli administration resulted in a significant release of thrombomodulin in a dose-dependent manner; however, thrombomodulin release was significantly attenuated (180 to 40 ng/mL) by anti-TNF pretreatment. This is parallel to the reduction of neutrophil activation (elastase). These results provide evidence for an E. coli dose-related and TNF-dependent thrombomodulin release into the plasma of septic baboons and suggest a possible role of anti-TNF in protection of the endothelium.
本研究旨在检测血栓调节蛋白是否在脓毒症狒狒中脱落，以及脱落是否被肿瘤坏死因子抗体（抗TNF）阻断。根据以下方案之一，将活的大肠杆菌静脉注射到24只狒狒体内：5×10⁸或2×10⁹ cfu/kg（n = 6/8），2×10⁹ cfu/kg加安慰剂（n = 5），或在注射大肠杆菌前2小时用1 mg/kg抗TNF预处理（n = 5）。大肠杆菌给药导致血栓调节蛋白以剂量依赖性方式显著释放；然而，抗TNF预处理可使血栓调节蛋白释放显著减弱（从180降至40 ng/mL）。这与中性粒细胞活化（弹性蛋白酶）的降低情况相似。这些结果为大肠杆菌剂量相关且TNF依赖的血栓调节蛋白释放到脓毒症狒狒血浆中提供了证据，并提示抗TNF在内皮保护中可能发挥作用。
