Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality
Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality
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DOI：
10.4049/jimmunol.177.3.1967
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Remick, Daniel G.
中科院分区：
文献类型：
--
作者：
Osuchowski, Marcin F.;Welch, Kathy;Remick, Daniel G.
脓毒症的死亡率仍然高得令人无法接受，调节炎症反应的尝试未能提高生存率。先前的报道认为败血症引发的免疫级联是多模态的：最初的全身炎症反应综合征（SIRS；过量的促炎介质，但没有/低抗炎血浆介质），中间的混合抗炎反应综合征（MARS；促炎介质和抗炎介质都有）和最终的代偿性抗炎反应综合征（CARS；过量的抗炎介质，但没有/低促炎介质）。为了验证这一点，我们通过对脓毒症动物重复采血来检查小鼠脓毒症早期炎症反应的演变。在早期死亡（1-5天）中观察到促炎（IL-6、TNF、IL-1 β、KC、MIP-2、MCP-1和eotaxin）和抗炎（TNF可溶性受体、IL-10、IL-1受体拮抗剂）细胞因子的血浆浓度升高。这些升高同时发生在促炎和抗炎介质中。血浆IL-6 （26 ng/ml）、TNF- α (12 ng/ml)、KC （33 ng/ml）、MIP-2 （14 ng/ml）、IL-1受体拮抗剂（65 ng/ml）、TNF可溶性受体1 （3 ng/ml）和TNF可溶性受体11 （14 ng/ml）水平准确预测24小时内的死亡率。相比之下，这些参数在晚期死亡（6-28天）或幸存者中均未升高。令人惊讶的是，促炎性或抗炎性细胞因子在预测预后前48小时的死亡率方面也是可靠的。这些数据表明，最初的炎症反应与早期而非晚期败血症死亡率直接相关。这种多方面的反应质疑使用一种简单的促炎细胞因子测量来分类脓毒症期间的炎症状态。
Mortality in sepsis remains unacceptably high and attempts to modulate the inflammatory response failed to improve survival. Previous reports postulated that the sepsis-triggered immunological cascade is multimodal: initial systemic inflammatory response syndrome (SIRS; excessive pro-, but no/low anti-inflammatory plasma mediators), intermediate homeostasis with a mixed anti-inflammatory response syndrome (MARS; both pro- and anti-inflammatory mediators) and final compensatory anti-inflammatory response syndrome (CARS; excessive anti-, but no/low proinflammatory mediators). To verify this, we examined the evolution of the inflammatory response during the early phase of murine sepsis by repetitive blood sampling of septic animals. Increased plasma concentrations of proinflammatory (IL-6, TNF, IL-1 beta, KC, MIP-2, MCP-1, and eotaxin) and anti-inflaminatory (TNF soluble receptors, IL-10, IL-1 receptor antagonist) cytokines were observed in early deaths (days 1-5). These elevations occurred simultaneously for both the pro- and anti-inflammatory mediators. Plasma levels of IL-6 (26 ng/ml), TNF-alpha (12 ng/ml), KC (33 ng/ml), MIP-2 (14 ng/ml), IL-1 receptor antagonist (65 ng/ml), TNF soluble receptor 1 (3 ng/ml), and TNF soluble receptor 11 (14 ng/ml) accurately predicted mortality within 24 h. In contrast, these parameters were not elevated in either the late-deaths (day 6-28) or survivors. Surprisingly, either pro- or anti-inflammatory cytokines were also reliable in predicting mortality up to 48 h before outcome. These data demonstrate that the initial inflammatory response directly correlates to early but not late sepsis mortality. This multifaceted response questions the use of a simple proinflammatory cytokine measurement for classifying the inflammatory status during sepsis.