Department of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan.
Crit Care. 2018 Jul 13;22(1):176. doi: 10.1186/s13054-018-2109-7.
Recent studies have suggested that excessive formation of neutrophil extracellular traps (NETs) plays a critical role in the pathogenesis of sepsis. Although elevation of the plasma level of cell-free DNA (cf-DNA) has been reported in sepsis patients, there has been little direct measurement of circulating free NETs such as myeloperoxidase-conjugated DNA (MPO-DNA). The objectives of this study were to detect NETs in the bloodstream of patients with septic shock, and to assess the correlations of circulating NET levels with organ dysfunction, disease severity, and mortality.
Fifty-five patients with septic shock admitted to the intensive care units (ICUs) of 35 Japanese hospitals were studied. Septic shock was diagnosed according to the 1997 definition of the American College of Chest Physicians/Society of Critical Care Medicine. To detect circulating NETs, plasma levels of MPO-DNA and cf-DNA were measured by sandwich enzyme-linked immunosorbent assay and by fluorometric assay on days 1, 3, and 7 after the onset of septic shock. Physiological and mortality data were collected from the clinical database.
On days 1, 3, and 7, the patients showed a marked increase in plasma MPO-DNA levels compared with healthy volunteers, whereas the plasma cf-DNA level was only increased significantly on day 1 and then decreased rapidly. A high MPO-DNA level on days 3 and 7 were associated with 28-day mortality. On days 3 and 7, the MPO-DNA levels were inversely correlated with both the mean arterial pressure and the PaO/FO ratio, whereas the cf-DNA level was not correlated with either parameter. There was a positive correlation between the plasma MPO-DNA level and the sepsis-related organ failure assessment score on days 3 and 7. Neither cf-DNA nor MPO-DNA levels were correlated with the disseminated intravascular coagulation (DIC) score or the platelet count.
The increase in circulating MPO-DNA in patients with septic shock indicates acceleration of NET formation in the early stages of sepsis. High MPO-DNA levels are associated with the severity of organ dysfunction and 28-day mortality due to septic shock, but not with the DIC score. These results suggest that excessive NET formation contributes to the pathogenesis of septic shock.
最近的研究表明，中性粒细胞胞外诱捕网（NETs）的过度形成在脓毒症发病机制中起着关键作用。虽然脓毒症患者的血浆无细胞 DNA（cf-DNA）水平升高已有报道，但对循环游离 NETs（如髓过氧化物酶结合 DNA（MPO-DNA））的直接测量却很少。本研究的目的是检测脓毒性休克患者的血流中 NETs，并评估循环 NET 水平与器官功能障碍、疾病严重程度和死亡率的相关性。
研究了 35 家日本医院重症监护病房（ICU）收治的 55 例脓毒性休克患者。根据美国胸科医师学院/危重病医学会 1997 年的定义诊断为脓毒性休克。为了检测循环 NETs，通过夹心酶联免疫吸附试验和荧光法在脓毒性休克发病后第 1、3 和 7 天测量 MPO-DNA 和 cf-DNA 的血浆水平。从临床数据库中收集生理和死亡率数据。
在第 1、3 和 7 天，与健康志愿者相比，患者的血浆 MPO-DNA 水平明显升高，而 cf-DNA 水平仅在第 1 天显著升高，然后迅速下降。第 3 和 7 天的高 MPO-DNA 水平与 28 天死亡率相关。第 3 和 7 天，MPO-DNA 水平与平均动脉压和 PaO/FO 比值呈负相关，而 cf-DNA 水平与这两个参数均无相关性。第 3 和 7 天，血浆 MPO-DNA 水平与脓毒症相关器官衰竭评估评分呈正相关。cf-DNA 或 MPO-DNA 水平与弥散性血管内凝血（DIC）评分或血小板计数均无相关性。
脓毒性休克患者循环 MPO-DNA 的增加表明脓毒症早期 NET 形成加速。高 MPO-DNA 水平与器官功能障碍的严重程度和脓毒性休克的 28 天死亡率相关，但与 DIC 评分无关。这些结果表明，NET 的过度形成导致了脓毒性休克的发病机制。
