Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents.
Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents.
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DOI：
10.1084/jem.173.4.1021
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发表时间：
1991-04-01
影响因子：
15.3
通讯作者：
Suffredini, A F
中科院分区：
文献类型：
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作者：
Martich, G D;Danner, R L;Ceska, M;Suffredini, A F
白细胞介素8（IL-8）是一种有效的中性粒细胞激活剂，可能在严重革兰氏阴性菌感染的早期宿主反应中起重要作用。IL-8与其他急性期细胞因子（肿瘤坏死因子α [TNF-α]，IL-6和IL-1 β）在25名正常人中进行了测量，这些人随机接受单独的静脉内毒素或口服布洛芬或戊茶碱后接受内毒素，布洛芬或戊茶碱是体外改变内毒素诱导的一些炎症反应的药物。TNF免疫反应性在1.5 h时达到最大值，给予内毒素/布洛芬的受试者的总TNF（曲线下面积）分别是给予内毒素单独（p = 0.026）或内毒素/布洛芬（p = 0.004）的受试者的4.2倍和4.5倍。IL-6水平在2-3小时达到最大值，三组之间没有差异。在任何受试者中均未检测到IL-1 β。在单独给予内毒素或给予内毒素/戊茶碱的受试者中，IL-8水平在2小时达到峰值，5小时降至基线水平。给予内毒素/布洛芬的受试者的IL-8升高更持久，与单独内毒素（p = 0.048）或内毒素/布洛芬（p = 0.023）相比，3 h时的峰值水平分别高出2.8倍和2.5倍。各组之间总IL-8释放的差异接近统计学显著性（ANOVA，p = 0.07）。该趋势反映了接受布洛芬的受试者与接受戊茶碱的受试者相比IL-8的释放增加（高1.9倍; p = 0.024）。这表明环氧合酶产物可能为体内细胞因子的产生提供重要的负反馈回路。循环IL-8的增加是人类对内毒素的急性炎症反应的一部分。败血症治疗引起的细胞因子反应的改变可能对败血症期间的宿主防御和损伤具有重要意义。
Interleukin 8 (IL-8), a potent activator of neutrophils, may be important in the early host response to serious Gram-negative infections. IL-8 was measured with other acute phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-6 and IL-1 beta) in 25 normal humans randomized to receive either intravenous endotoxin alone or endotoxin after oral administration of ibuprofen or pentoxifylline, agents that alter some of the inflammatory responses induced by endotoxin in vitro. TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively. IL-6 levels were maximum at 2-3 h and did not differ among the three groups. No IL-1 beta was detected in any subject. IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h. Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively. Differences in total IL-8 release among groups approached statistical significance (ANOVA, p = 0.07). This trend reflected the increased release of IL-8 by the subjects receiving ibuprofen compared to pentoxifylline (1.9-fold higher; p = 0.024). This suggests that cyclooxygenase products may provide important negative feedback loops for cytokine production in vivo. Increases in circulating IL-8 are part of the acute inflammatory response of humans to endotoxin. Altered cytokine responses caused by antiinflammatory therapy may have important implications for both host defense and injury during septicemia.