Margraf Stefan, Lögters Tim, Reipen Jenny, Altrichter Jens, Scholz Martin, Windolf Joachim
Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Shock. 2008 Oct;30(4):352-8. doi: 10.1097/SHK.0b013e31816a6bb1.
The release of "neutrophil extracellular traps" (NETs) has been identified as a novel immune response in innate immunity. Neutrophil extracellular traps are composed of neutrophil-derived circulating free DNA (cf-DNA), histones, and neutrophil cytoplasm-derived proteins such as proteases. Here, we studied the putative predictive value of plasma cf-DNA/NETs for the development of sepsis and mortality after multiple trauma. In a prospective pilot study with 45 multiple trauma (Injury Severity Score>16) patients, cf-DNA was directly quantified in plasma. Blood samples were sequentially obtained daily from admission to our Trauma Center until day 10. Because of limited intensive care unit (ICU) stay of less than 3 days, 8 patients have been excluded, resulting in 37 patients that were evaluated. Time kinetics of cf-DNA/NETs was compared with C-reactive protein (CRP), interleukin (IL) 6, leukocyte counts, and myeloperoxidase. The severity of the injury was calculated on the basis of the Injury Severity Score, as well as Multiple Organ Dysfunction Score, Sequential Organ Failure Assessment, and Simplified Acute Physiology Score II on ICU. Initially high cf-DNA/NETs values (>800 ng/mL) with recurrent increased values between days 5 to 9 were associated with subsequent sepsis, multiple organ failure, and death. In conjunction with cf-DNA/NETs, IL-6 was significantly elevated after admission. However, the development of a second hit was not indicated by IL-6. In contrast to cf-DNA/NETs, no difference in CRP kinetics was observed between patients with and without development of sepsis. Circulating free DNA/NETs kinetics rather followed kinetics of Multiple Organ Dysfunction Score, Sepsis-related Organ Failure Assessment, leukocyte counts, and partially of myeloperoxidase. Circulating free DNA/NETs seems to be a valuable additional marker for the calculation of injury severity and/or prediction of inflammatory second hit on ICU. However, a large clinical trial with severely injured patients should confirm the prognostic value of neutrophil-derived cf-DNA/NETs.
“中性粒细胞胞外陷阱”（NETs）的释放已被确定为固有免疫中的一种新型免疫反应。中性粒细胞胞外陷阱由中性粒细胞衍生的循环游离DNA（cf-DNA）、组蛋白以及中性粒细胞胞质衍生的蛋白质（如蛋白酶）组成。在此，我们研究了血浆cf-DNA/NETs对多发伤后脓毒症发生及死亡率的潜在预测价值。在一项针对45例多发伤（损伤严重度评分>16）患者的前瞻性初步研究中，对血浆中的cf-DNA进行了直接定量。从患者入住我们的创伤中心开始，每天依次采集血样，直至第10天。由于8例患者在重症监护病房（ICU）的停留时间不足3天而被排除，最终对37例患者进行了评估。将cf-DNA/NETs的时间动力学与C反应蛋白（CRP）、白细胞介素（IL）-6、白细胞计数和髓过氧化物酶进行了比较。根据损伤严重度评分以及ICU中的多器官功能障碍评分、序贯器官衰竭评估和简化急性生理学评分II来计算损伤的严重程度。最初较高的cf-DNA/NETs值（>800 ng/mL）以及在第5至9天期间反复升高的值与随后发生的脓毒症、多器官功能衰竭和死亡相关。与cf-DNA/NETs一起，入院后IL-6显著升高。然而，IL-6并未提示二次打击的发生。与cf-DNA/NETs不同，发生脓毒症和未发生脓毒症的患者之间CRP动力学没有差异。循环游离DNA/NETs动力学更符合多器官功能障碍评分、脓毒症相关器官衰竭评估、白细胞计数以及部分髓过氧化物酶的动力学。循环游离DNA/NETs似乎是计算损伤严重程度和/或预测ICU中炎症二次打击的一个有价值的附加标志物。然而，一项针对重伤患者的大型临床试验应证实中性粒细胞衍生的cf-DNA/NETs的预后价值。
