Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes.
Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes.
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DOI：
10.1097/ccm.0000000000002014
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发表时间：
2017-01
影响因子：
8.8
通讯作者：
Baron RM
中科院分区：
文献类型：
--
作者：
Dalli J;Colas RA;Quintana C;Barragan-Bradford D;Hurwitz S;Levy BD;Choi AM;Serhan CN;Baron RM
脓毒症造成严重的社会经济负担，发病率和死亡率都很高。最近描述的化学介质，称为专门的促解决介质，积极调节急性炎症的解决。在本研究中，我们从脓毒症患者（n=22名受试者）的重症监护室（ICU）入院48小时内以及之后的第3天和第7天收集去鉴定血浆，并进行脂质介质（LM）分析。在所有患者中，我们使用花生四烯酸、二十碳五烯酸和二十二碳六烯酸代谢组的既定标准，在外周血中鉴定了bb30种生物活性介质和途径标记物。其中包括炎症启动介质白三烯（LT）B4和前列腺素（PG）E2以及促溶解介质resolvin (Rv) D1， RvD2和保护素（PD）1。在脓毒症非幸存者中，我们发现炎症启动介质包括PGF2α和LTB4以及促溶解介质包括RvE1， RvD5和17R-PD1明显高于存活的脓毒症患者。这一特征在ICU入院时出现并持续了7天。进一步分析显示，非幸存者呼吸衰竭增加。较高的炎症启动介质（包括PGF2α）和一些促缓解途径与ARDS的发展有关，而其他传统临床指标不能预测ARDS的发展。这些结果提供了脓毒症中与生存和ARDS发展相关的外周血脂介质谱，从而为危重疾病提供了可信的新生物标志物和生物靶点。
Sepsis produces a major socio-economic burden with significant morbidity and mortality. Recently described chemical mediators, termed specialized pro-resolving mediators, actively regulate the resolution of acute-inflammation. Herein, de-identified plasma was collected from sepsis patients (n=22 subjects) within 48h of admission to the Intensive Care Unit (ICU) and on days 3 and 7 thereafter and subjected to lipid mediator (LM) profiling. In all patients, we identified > 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene (LT)B4 and prostaglandin (PG)E2 and pro-resolving mediators resolvin (Rv) D1, RvD2, and protectin (PD)1. In sepsis non-survivors we found significantly higher inflammation-initiating mediators including PGF2α and LTB4 and pro-resolving mediators including RvE1, RvD5 and 17R-PD1 than was observed in surviving sepsis subjects. This signature was present at ICU admission and persisted for 7 days. Further analysis revealed increased respiratory failure in non-survivors. Higher inflammation-initiating mediators (including PGF2α) and select pro-resolving pathways were associated with the development of ARDS, while other traditional clinical indices were not predictive of ARDS development. These results provide peripheral blood lipid mediator profiles in sepsis that correlate with survival and ARDS development, thus suggesting plausible novel biomarkers and biologic targets for critical illness.