Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Shock. 2021 Oct 1;56(4):544-550. doi: 10.1097/SHK.0000000000001753.
Levels of the apoptosis regulator Fas ligand (FasL) are associated with severity of sepsis, but its association with the mortality of sepsis and necroptosis, a regulated cell death mechanism, is not yet clear. We aimed to assess the association of FasL level with outcomes of sepsis and receptor interacting protein kinase-3 (RIPK3), an essential necroptosis mediator, for determining the relationship between FasL and necroptosis.
Plasma FasL and RIPK3 levels were measured by ELISA from prospectively enrolled critically ill adult patients. The best cut-off level of FasL for 28-day mortality prediction was determined by Youden's index. The association between plasma levels of FasL and RIPK3 was assessed by a linear regression method.
Among 188 patients, 58 (30.9%) were diagnosed with sepsis and 84 (44.7%) with septic shock, respectively. Plasma levels of FasL increased in the group order of control, sepsis, and septic shock groups (P for trend < 0.001). For 142 patients with sepsis, organ dysfunction and septic shock were more prevalent in the group with plasma FasL levels that were higher than the best cut-off level. A significant difference in mortality between high and low FasL patients was observed up to 90 days (Log-rank P = 0.013). FasL levels did not significantly change over day 3 and day 7. FasL levels were not correlated with those of RIPK3.
The plasma level of FasL was associated with severity of sepsis and was predictive of mortality. However, it was not correlated with RIPK3 level.
凋亡调节因子 Fas 配体 (FasL) 的水平与脓毒症的严重程度相关，但它与脓毒症死亡率和坏死性凋亡（一种受调控的细胞死亡机制）的关系尚不清楚。我们旨在评估 FasL 水平与脓毒症结局的关系，以及受体相互作用蛋白激酶-3 (RIPK3)（一种重要的坏死性凋亡介质），以确定 FasL 与坏死性凋亡之间的关系。
通过酶联免疫吸附试验（ELISA）从前瞻性纳入的危重症成年患者中测量血浆 FasL 和 RIPK3 水平。通过 Youden 指数确定 FasL 预测 28 天死亡率的最佳截断值。通过线性回归方法评估 FasL 和 RIPK3 之间的血浆水平相关性。
在 188 名患者中，分别有 58 名（30.9%）被诊断为脓毒症和 84 名（44.7%）为感染性休克。FasL 血浆水平在对照组、脓毒症组和感染性休克组中呈递增组序（趋势 P < 0.001）。在 142 名脓毒症患者中，高 FasL 组比低 FasL 组更易发生器官功能障碍和感染性休克。高 FasL 和低 FasL 患者的死亡率在 90 天内有显著差异（Log-rank P = 0.013）。FasL 水平在第 3 天和第 7 天没有明显变化。FasL 水平与 RIPK3 水平不相关。
FasL 血浆水平与脓毒症的严重程度相关，并可预测死亡率。然而，它与 RIPK3 水平不相关。
