Regulation of adhesion molecules during human endotoxemia - No acute effects of aspirin
Regulation of adhesion molecules during human endotoxemia - No acute effects of aspirin
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DOI：
10.1164/ajrccm.159.3.9805087
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发表时间：
1999-03-01
影响因子：
24.7
通讯作者：
Wagner, OF
中科院分区：
文献类型：
--
作者：
Jilma, B;Blann, A;Wagner, OF
革兰氏阴性败血性休克部分是由内毒素（脂多糖；LPS）介导的，动物模型表明，即使是单个粘附分子的阻断也可显着提高生存率。因此，干扰粘附级联可能为人类脓毒症提供有用的治疗方法。年轻健康男性 (n = 30) 每人静脉注射 4 ng/kg LPS，以研究内毒素血症对人体粘附过程的影响，并确定药物干预的潜在目标。三分之一的受试者接受了 1,000 毫克阿司匹林和 1,000 毫克扑热息痛的预处理，以研究阿司匹林的潜在抗炎作用或退热作用。 LPS 后 67 分钟，循环中性粒细胞下降 -80%，单核细胞在 90 分钟下降 -96%，淋巴细胞在 240 分钟下降 -85%。 L-选择素表达降低，特别是在单核细胞上。循环 (c)E-选择素水平增加了 820%，血管性血友病因子-Ag (VWF)、可溶性血栓调节蛋白、循环 (c)P-选择素、循环细胞间粘附分子-1 (cICAM-1) 和循环血管细胞粘附分子-1 (cVCAM-1) 水平平均增加 65% 至 98%（p < 0.001），但 cL-选择素仅增加 15%。可溶性粘附分子的尿液排泄可以忽略不计。阿司匹林对 LPS 引起的粘附参数变化没有影响，但扑热息痛减弱了 vWF 的相对增加，同时对其他测量参数没有影响。内毒素血症期间 cE-选择素的一致、深刻和早期上调表明，与其他测量的标记物相比，cE-选择素可能是监测全身炎症中内皮细胞活化状态的更好的替代标记物。尽管阿司匹林在此模型中没有任何抗炎作用，但扑热息痛降低了 vWF 的相对增加。
Gram-negative septic shock is mediated in part by endotoxin (lipopolysaccharide; LPS), and animal models have shown that blockade of even single adhesion molecules considerably improves survival. Thus interference with the adhesion cascade may provide a useful therapeutic approach in human sepsis. Young healthy men (n = 30) each received a bolus of 4 ng/kg LPS intravenously to study the effects of endotoxemia on adhesion processes in humans and to identify potential targets for pharmacologic intervention. One third of subjects received pretreatment with 1,000 mg aspirin and 1,000 mg paracetamol to study potential antiinflammatory effects of aspirin or effects of antipyresis. Circulating neutrophils dropped by -80% at 67 min after LPS, monocytes by -96% at 90 min, and lymphocytes by -85% at 240 min. L-selectin expression decreased, particularly on monocytes. Circulating (c)E-selectin levels increased by 820%, von Willebrand factor-Ag (VWF), soluble thrombomodulin, circulating (c)P-selectin, circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular cell adhesion molecule-1 (cVCAM-1) by a mean of 65 to 98% (p < 0.001 for all), but cL-selectin by only 15%. Urinary excretion of soluble adhesion molecules was negligible. Aspirin had no influence on the LPS-induced changes of adhesion parameters, but paracetamol blunted the relative increase in vWF while having no effects on the other parameters measured. The consistent, profound, and early upregulation of cE-selectin during endotoxemia indicates that cE-selectin may be a better surrogate marker to monitor the activation status of endothelial cells in systemic inflammation than the other markers measured. Although aspirin did not have any antiinflammatory effects in this model, paracetamol lowered the relative increase in vWF.