败血症
生物标志物
医学
内科学
器官功能障碍
程序性细胞死亡
心脏病学
生物
细胞凋亡
生物化学
作者
Edward J. Schenck,C. Kevin,David R. Price,Thomas Nicholson,Clara Oromendia,Eliza Gentzler,Elizabeth Sánchez,Rebecca M. Baron,Laura E. Fredenburgh,Jin Won Huh,Ilias Ι. Siempos,Augustine M.K. Choi
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2019-05-02
卷期号:4 (9)
被引量:39
标识
DOI:10.1172/jci.insight.127143
摘要
In sepsis, there may be dysregulation in programed cell death pathways, typified by apoptosis and necroptosis. Programmed cell death pathways may contribute to variability in the immune response. TRAIL is a potent inducer of apoptosis. Receptor-interacting serine/threonine protein kinase-3 (RIPK3) is integral to the execution of necroptosis. We explored whether plasma TRAIL levels were associated with in-hospital mortality, organ dysfunction, and septic shock. We also explored the relationship between TRAIL and RIPK3.We performed an observational study of critically ill adults admitted to intensive care units at 3 academic medical centers across 2 continents, using 1 as derivation and the other 2 as validation cohorts. Levels of TRAIL were measured in the plasma of 570 subjects by ELISA.In all cohorts, lower (<28.5 pg/ml) versus higher levels of TRAIL were associated with increased organ dysfunction (P ≤ 0.002) and septic shock (P ≤ 0.004). Lower TRAIL levels were associated with in-hospital mortality in 2 of 3 cohorts (Weill Cornell-Biobank of Critical Illness, P = 0.012; Brigham and Women's Hospital Registry of Critical Illness, P = 0.011; Asan Medical Center, P = 0.369). Lower TRAIL was also associated with increased RIPK3 (P ≤ 0.001).Lower levels of TRAIL were associated with septic shock and organ dysfunction in 3 independent ICU cohorts. TRAIL was inversely associated with RIPK3 in all cohorts.NIH (R01-HL055330 and KL2-TR002385).
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