Department of Immunopathology, Sanquin Research at CLB and Landsteiner Laboratory of the AMC, Amsterdam, The Netherlands.
Crit Care Med. 2012 Dec;40(12):3224-9. doi: 10.1097/CCM.0b013e318265695f.
Cell death leading to circulating nucleosomes and histones is a critical step in the pathogenesis of sepsis and contributes to lethality. Activated protein C was demonstrated to attenuate the harmful effects of histones. The objective of this retrospective study was to evaluate whether nucleosomes correlate with the severity of the inflammatory response and mortality in children suffering from severe meningococcal sepsis. Furthermore, we wanted to study the effects of infusion of protein C on nucleosome levels in children with septic purpura.
Retrospective analysis of nucleosome levels in children suffering from meningococcal sepsis treated with either placebo or protein C.
Pediatric intensive care unit of a tertiary care university center.
In a randomized, placebo-controlled study, either protein C or placebo was administered to 38 children suffering from meningococcal sepsis. Nucleosome levels have been measured retrospectively in these 38 children suffering from meningococcal sepsis.
Twenty-eight children were treated with protein C and 10 received placebo. Nucleosome levels were significantly higher in nonsurvivors (n = 9) at any time point measured as compared to survivors (n = 29). Nucleosome levels significantly correlated with organ dysfunction scores, cytokines, and parameters for coagulation. Patients treated with protein C had significantly higher activated protein C levels than children receiving placebo. We could not find a clear effect of activated protein C on nucleosome levels in these patients.
Circulating nucleosomes correlated with the severity of the inflammatory response and were associated with mortality in children suffering from meningococcal sepsis. We show that protein C administration does not decrease nucleosome levels in these patients.
导致循环核小体和组蛋白的细胞死亡是脓毒症发病机制中的一个关键步骤，并导致死亡率升高。已证实活化蛋白 C 可减轻组蛋白的有害作用。本回顾性研究的目的是评估核小体是否与患有严重脑膜炎球菌性败血症的儿童的炎症反应严重程度和死亡率相关。此外，我们还研究了在患有脓毒性紫癜的儿童中输注蛋白 C 对核小体水平的影响。
对接受安慰剂或蛋白 C 治疗的患有脑膜炎球菌性败血症的儿童的核小体水平进行回顾性分析。
三级护理大学中心的儿科重症监护病房。
在一项随机、安慰剂对照研究中，38 例患有脑膜炎球菌性败血症的儿童接受了蛋白 C 或安慰剂治疗。回顾性测量了这 38 例患有脑膜炎球菌性败血症的儿童的核小体水平。
28 例患儿接受蛋白 C 治疗，10 例患儿接受安慰剂治疗。与存活者（n = 29）相比，任何时间点的死亡者（n = 9）的核小体水平均显著升高。核小体水平与器官功能障碍评分、细胞因子和凝血参数显著相关。接受蛋白 C 治疗的患者的活化蛋白 C 水平明显高于接受安慰剂的患者。我们没有发现活化蛋白 C 对这些患者的核小体水平有明显影响。
循环核小体与炎症反应的严重程度相关，并与患有脑膜炎球菌性败血症的儿童的死亡率相关。我们表明，蛋白 C 给药并不能降低这些患者的核小体水平。
