Intensive Care Unit, Hospital Universitario Principe de Asturias, Alcala de Henares, Madrid, Spain.
J Intensive Care Med. 2011 Mar-Apr;26(2):125-32. doi: 10.1177/0885066610384465.
Mortality in patients with septic shock remains unacceptably high and the attempts to antagonize certain proinflammatory cytokines based on the results of animal model studies have failed to improve survival rates. The objective of this article is to examine the pro-/anti-inflammatory cytokine balance in patients with septic shock and its connection with mortality.
Serum levels of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin 1β [IL-1β], interferonγ [IFN-γ], and IL-6) and soluble cytokine antagonists (soluble TNF receptor I [sTNF-RI], sTNF-RII, and IL-1Ra) were determined on admission to the intensive care unit (ICU) and 3, 7, 14, and 28 days later in 52 patients with septic shock and in 36 healthy controls. Specific sandwich enzyme-linked immunosorbent assay (ELISA) was used for all determinations.
Serum levels of most of the pro- and anti-inflammatory molecules examined (TNF-α, IL-6, sTNF-RI, sTNF-RII, and IL-1 receptor agonist [IL-1Ra]) were significantly elevated on admission and during the 28-day observation period in patients when compared to controls. Notably, the anti-inflammatory mediators sTNF-RI, sTNF-RII, and IL-1Ra were better predictors of mortality. Receiver-operating characteristic (ROC) analysis revealed that sTNF-RI or sTNF-RII concentrations over 2767 or 4619 pg/mL, respectively, determined a high risk of death (sensitivity: 100%-100%, specificity: 57.1%-71.4%, area under the curve [AUC] 0.759-0.841, respectively), whereas IL-1Ra concentrations below 7033 pg/mL determined a high probability of survival (sensitivity: 60%, specificity: 100%, AUC 0.724). In addition, IFN-γ levels were significantly higher in survivors than in controls during the initial 2 weeks of observation.
Our data show that serum cytokine disturbance patterns have prognostic significance in patients with septic shock admitted to the ICU. The pattern, defined by an early response to continuously elevated anti-inflammatory cytokine serum levels, is associated with an enhanced risk of a fatal outcome for patients.
脓毒性休克患者的死亡率仍然高得令人无法接受，基于动物模型研究结果拮抗某些促炎细胞因子的尝试未能提高生存率。本文的目的是研究脓毒性休克患者的促炎/抗炎细胞因子平衡及其与死亡率的关系。
在 52 例脓毒性休克患者和 36 例健康对照者入住重症监护病房（ICU）时、第 3、7、14 和 28 天，分别测定血清中促炎细胞因子（肿瘤坏死因子-α[TNF-α]、白细胞介素 1β[IL-1β]、干扰素-γ[IFN-γ]和白细胞介素 6[IL-6]）和可溶性细胞因子拮抗剂（可溶性 TNF 受体 I[sTNF-RI]、sTNF-RII 和 IL-1 受体拮抗剂[IL-1Ra]）的水平。所有测定均采用特定的夹心酶联免疫吸附试验（ELISA）。
与对照组相比，大多数检查的促炎和抗炎分子（TNF-α、IL-6、sTNF-RI、sTNF-RII 和白细胞介素 1 受体激动剂[IL-1Ra]）在入院时和 28 天观察期内的血清水平均显著升高。值得注意的是，抗炎介质 sTNF-RI、sTNF-RII 和 IL-1Ra 是死亡率的更好预测因子。接收者操作特征（ROC）分析显示，sTNF-RI 或 sTNF-RII 浓度分别超过 2767 或 4619pg/ml，分别确定了死亡的高风险（敏感性：100%-100%，特异性：57.1%-71.4%，曲线下面积[AUC]0.759-0.841），而 IL-1Ra 浓度低于 7033pg/ml 确定了高存活率（敏感性：60%，特异性：100%，AUC 0.724）。此外，在最初的 2 周观察期间，IFN-γ 水平在幸存者中明显高于对照组。
我们的数据表明，ICU 收治的脓毒性休克患者的血清细胞因子紊乱模式具有预后意义。这种模式由对持续升高的抗炎细胞因子血清水平的早期反应定义，与患者致命结局的风险增加相关。
