Shedding kinetics of soluble tumor necrosis factor (TNF) receptors after systemic TNF leaking during isolated limb perfusion - Relevance to the pathophysiology of septic shock
Shedding kinetics of soluble tumor necrosis factor (TNF) receptors after systemic TNF leaking during isolated limb perfusion - Relevance to the pathophysiology of septic shock
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DOI：
10.1172/jci694
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发表时间：
1998-02-01
影响因子：
15.9
通讯作者：
Klausner, J
中科院分区：
文献类型：
--
作者：
Aderka, D;Sorkine, P;Klausner, J
我们研究了在离体肢体灌流过程中可溶性TNF受体（TNF-Rs）对TNF渗漏的反应动力学，并将其与所产生的血流动力学效应相关联，在TNF渗漏进入体循环后7 min开始释放TNF-Rs，在体内和细胞培养中均观察到三波释放，峰值分别出现在1、8-12和48-72 h。可溶性受体使TNF在体循环中的半衰期延长至2.5 ~ 6 h，p75在第一波中比p55 TNF-Rs有更多的释放，释放的量和速度与血清TNF水平成正比（P < 0.001），只有在TNF浓度接近1.5ng/ml时，第一波脱落才达到最大脱落量。在此水平以上，TNF与其可溶性受体之间的线性关系消失，TNF诱导的低血压与TNF与其可溶性受体之间的初始失衡相一致。尽管自发纠正这种不平衡在8-12小时，血流动力学和生化改变持续存在，并在18小时进一步加重，这表明，其他因素引起的TNF早期负责的血流动力学不稳定的永久化。这项研究可能提供一个更生理治疗方法的基础上，TNF中和感染性休克患者。
We examined the kinetics of shedding of the soluble TNF receptors (TNF-Rs) in response to TNF leakage during isolated limb perfusion procedures and correlated them to the resulting hemodynamic effects.Shedding of the TNF-Rs started 7 min after TNF leakage into the systemic circulation, Three waves of shedding were observed peaking at 1, 8-12, and 48-72 h both in vivo and in cell cultures. The soluble receptors prolonged the half-life of TNF in the systemic circulation to 2.5-6 h, Excess shedding of the p75 compared with p55 TNF-Rs was noted during the first wave, The amount and speed of shedding of the p75 TNF-Rs were proportional to the serum TNF levels (P < 0.001), A maximal shedding capacity was attained only during the first wave of shedding, at TNF concentrations of similar to 1.5 ng/ml. Above this level, the linearity between TNF and its soluble receptors was lost, TNF-induced hypotension coincided with the initial imbalance bet between the concentrations of TNF and its soluble receptors. Despite the spontaneous correction of this imbalance at 8-12 h, the hemodynamic and biochemical alterations persisted and were further aggravated at 18 h, suggesting that other factors induced earlier by TNF are responsible for the perpetuation of the hemodynamic instability.This study may provide the basis for a more physiological therapeutic approach to TNF neutralization in septic shock patients.