Inflammasome mRNA expression in human monocytes during early septic shock
Inflammasome mRNA expression in human monocytes during early septic shock
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DOI：
10.1164/rccm.200703-418oc
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发表时间：
2008-05-01
影响因子：
24.7
通讯作者：
Wewers, Mark D.
中科院分区：
文献类型：
--
作者：
Fahy, Ruairi J.;Exline, Matthew C.;Wewers, Mark D.
原理：单核细胞是脓毒症炎症反应启动的核心，其中caspase-1激活发挥关键作用。脓毒症时单核细胞失活与不良预后有关。目的：鉴于caspase-1在免疫应答中的重要性，我们研究了脓毒症休克早期患者的单核细胞是否表现出caspase-1相关分子mRNA的改变。研究对象为健康志愿者（n = 22）、重症监护室患者（n = 26;年龄> 18岁）、重症监护室患者（n = 20）和健康志愿者（n = 22）。获得人口统计学、生物学、生理学和血浆细胞因子测量结果。测定单核细胞的离体肿瘤坏死因子-α产生，并通过定量逆转录聚合酶链反应分析新鲜单核细胞mRNA的Toll样受体、NOD-LRR蛋白、细胞因子和核因子-κ B相关基因。ASC、半胱天冬酶-1、NALP 1的炎性体mRNA的相对拷贝数，和Pypaf-7在感染性休克患者中显著低于重症对照受试者。NALP 1 mRNA水平与脓毒症患者的生存率相关（P = 0.0068），与SAPS II评分相关（r = -0.63）。结论：这些数据表明，单核细胞失活发生在全身炎症反应的最早阶段，炎性体mRNA表达的变化是这一过程的一部分。
Rationale: Monocytes are central to the initiation of the inflammatory response in sepsis, with caspase-1 activation playing a key role. Monocyte deactivation during sepsis has been linked to poor outcomes.Objectives: Given the importance of caspase-1 in the immune response, we investigated whether monocytes from patients early in septic shock demonstrate alterations in mRNAs for caspase-1-related molecules.Methods: Patients with septic shock (n = 26; age >18years), critically ill intensive care unit patients (n = 20), and healthy volunteers (n = 22) were enrolled in a prospective cohort study in a university intensive care unit. Demographic, biological, physiologic, and plasma cytokine measurements were obtained. Monocytes were assayed for ex vivo tumor necrosis factor-a production, and fresh monocyte mRNA was analyzed by quantitative reverse-transcription polymerase chain reaction for Toll-like receptors, NOD-LRR proteins, cytokines, and nuclear factor-kappa B-related genes.Measurements and Main Results: Relative copy numbers for the inflammasome mRNAs for ASC, caspase-1, NALP1, and Pypaf-7 were significantly lower in patients with septic shock compared with critically ill control subjects. NALP1 mRNA levels were linked to survival in patients with sepsis (P = 0.0068) and correlated with SAPS II scores (r = -0.63).Conclusions: These data suggest that monocyte deactivation occurs during the earliest stages of the systemic inflammatory response and that changes in inflammasome mRNA expression are part of this process.