Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis.
Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis.
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发表时间：
1992-02
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通讯作者：
J. Nuijens;J. Abbink;Y. Wachtfogel;R. Colman;A. Eerenberg;D. Dors;Kamp Aj;Strack van Schijndel Rj;Thijs Lg;C. Hack
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作者：
J. Nuijens;J. Abbink;Y. Wachtfogel;R. Colman;A. Eerenberg;D. Dors;Kamp Aj;Strack van Schijndel Rj;Thijs Lg;C. Hack
增加的血管通透性和血管舒张，可能是内皮扰动的结果，被认为是感染性休克的基本发病机制之一。中性粒细胞被认为是内皮损伤介质的来源。我们测量了弹性蛋白酶-α 1-抗胰蛋白酶（α 1 AT）复合物和乳铁蛋白作为标志物，用于脓毒症患者入住重症监护室时血浆中中性粒细胞颗粒内容物的释放，并描述了中性粒细胞活化与其他炎症参数以及血液动力学和生化参数的关系。弹性蛋白酶-α 1AT和乳铁蛋白水平彼此显著相关（r = 0.58; p <0.008），分别有96%和71%的患者升高（分别大于3.33和5 nmol/L）。乳铁蛋白（而非弹性蛋白酶-α 1 AT）与白色血细胞数量相关（r = 0.38; p = 0.008）。与无血压异常的患者相比，休克患者的弹性蛋白酶-α 1 AT水平显著较高（p = 0.008），而白色血细胞计数较低（p = 0.015）。弹性蛋白酶-α 1AT和乳铁蛋白水平均与乳酸水平相关（r = 0.33; p = 0.024和r = 0.30; p = 0.04），表明中性粒细胞活化在缺氧发病机制中的作用。此外，弹性蛋白酶-α 1AT与白细胞介素6（IL-6）（r = 0.46; p = 0.001）和C3 a（r = 0.38; p = 0.009）的浓度相关，表明细胞因子和补体可能有助于脓毒症中性粒细胞的脱粒。弹性蛋白酶-α 1AT复合物与C1抑制剂（r = -0.33; p = 0.028）和血小板数量（r = -0.42; p = 0.003）呈负相关。血浆中弹性蛋白酶-α 1AT复合物的水平似乎具有预后意义; 27例死亡患者的水平高于21例存活患者（p = 0.01）。浓度低于10 nM的27例患者的死亡率为37%，而浓度较高的21例患者的死亡率为81%。本研究的总死亡率为56%。这些结果提供了进一步的证据表明，中性粒细胞的激活和脱粒，诱导多种激动剂，参与发展中国家的致命并发症，脓毒症患者。
Increased vasopermeability and vasodilation, presumably the result of endothelial perturbation, are considered among the basic pathogenetic mechanisms in septic shock. Neutrophils have been implicated as a source for mediators in endothelial injury. We measured elastase-alpha 1-antitrypsin (alpha 1AT) complexes and lactoferrin as markers for release of neutrophil granule contents in plasma from patients with sepsis on admission to the Intensive Care Unit, and we delineated the relationship of neutrophil activation to other inflammatory parameters and to hemodynamic and biochemical parameters. Levels of elastase-alpha 1AT and lactoferrin significantly correlated with each other (r = 0.58; p less than 0.008), and were increased (greater than 3.33 and 5 nmol/L, respectively) in 96% and 71% of the patients, respectively. Lactoferrin, but not elastase-alpha 1AT, correlated with the number of white blood cells (r = 0.38; p = 0.008). Elastase-alpha 1 AT levels were significantly higher (p = 0.008), whereas white blood cell counts were lower (p = 0.015) in patients with shock when compared with patients without abnormal blood pressure. Both elastase-alpha 1AT and lactoferrin levels correlated with lactate levels (r = 0.33; p = 0.024 and r = 0.30; p = 0.04), suggesting a role for neutrophil activation in the pathogenesis of hypoxygenation. In addition, elastase-alpha 1AT correlated with the concentrations of interleukin 6 (IL-6) (r = 0.46; p = 0.001) and C3a (r = 0.38; p = 0.009), suggesting that cytokines and complement may contribute to the degranulation of neutrophils in sepsis. Elastase-alpha 1AT complexes were inversely related to C1-inhibitor (r = -0.33; p = 0.028) and to platelet numbers (r = -0.42; p = 0.003). Levels of elastase-alpha 1AT complexes in plasma appeared to be of prognostic significance; levels were higher in 27 patients who died than in 21 patients who survived (p = 0.01). The mortality in 27 patients with concentrations below 10 nM was 37%, whereas it was 81% in 21 patients with higher levels. The overall mortality in this study was 56%. These results provide further evidence that activation and degranulation of neutrophils, induced by multiple agonists, are involved in the development of fatal complications in patients with sepsis.