Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis/septic shock in the emergency department.
Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis/septic shock in the emergency department.
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DOI：
10.1371/journal.pone.0110678
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Brown SG
中科院分区：
文献类型：
--
作者：
Macdonald SP;Stone SF;Neil CL;van Eeden PE;Fatovich DM;Arendts G;Brown SG
识别急诊科 (ED) 区分严重脓毒症/脓毒性休克与单纯性脓毒症的生物标志物。脓毒症患者接受了连续血液采样，包括到达急诊室以及最初 24 小时内最多三个后续时间点。使用定量 PCR 测量外周血白细胞中代表先天免疫反应、器官功能障碍或休克的 13 个基因的信使 RNA (mRNA) 水平，并与健康对照进行比较。然后在每个时间点测量在无并发症的脓毒症和严重脓毒症/脓毒性休克之间差异表达的靶标的血清蛋白浓度，并在两个患者组之间进行比较。 27 名参与者（中位年龄 66 岁，(IQR 35, 78)）中，10 名患有无并发症的脓毒症，17 名患有脓毒症并伴有器官衰竭（14 名患有脓毒症休克；3 名患有其他脓毒症相关器官衰竭）。在急诊科首次采集样本时，严重脓毒症中白细胞介素 (IL)-10 和中性粒细胞明胶酶相关脂质运载蛋白 (NGAL) 的基因表达显着高于无并发症的脓毒症。任何靶基因的表达均未随时间发生显着变化。在急诊科首次采集样本时，严重脓毒症患者的 IL-6、IL-8、IL-10、NGAL 和 Resistin 血清浓度显着高于无并发症脓毒症，但在就诊后 24 小时内的所有时间点，与无并发症脓毒症相比，严重脓毒症中只有 IL-8、NGAL 和 Resistin 始终高于无并发症脓毒症。这些介质由受损组织和循环白细胞产生，可能在严重脓毒症的发展中发挥重要作用。进一步的工作将确定除了临床风险参数之外，它们对于早期识别随后病情恶化和/或死亡风险较高的患者是否具有任何价值。
To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED). Patients with sepsis underwent serial blood sampling, including arrival in the ED and up to three subsequent time points over the first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms of the innate immune response, organ dysfunction or shock were measured in peripheral blood leucocytes using quantitative PCR, and compared with healthy controls. Serum protein concentrations of targets differentially expressed between uncomplicated sepsis and severe sepsis/septic shock were then measured at each time point and compared between the two patient groups. Of 27 participants (median age 66 years, (IQR 35, 78)), 10 had uncomplicated sepsis and 17 had sepsis with organ failure (14 septic shock; 3 had other sepsis-related organ failures). At the time of first sample collection in the ED, gene expression of Interleukin (IL)-10 and Neutrophil Gelatinase Associated Lipocalin (NGAL) were significantly higher in severe sepsis than uncomplicated sepsis. Expression did not significantly change over time for any target gene. Serum concentrations of IL-6, IL-8, IL-10, NGAL and Resistin were significantly higher in severe sepsis than uncomplicated sepsis at the time of first sample collection in the ED, but only IL-8, NGAL and Resistin were consistently higher in severe sepsis compared to uncomplicated sepsis at all time points up to 24 h after presentation. These mediators, produced by both damaged tissues and circulating leukocytes, may have important roles in the development of severe sepsis. Further work will determine whether they have any value, in addition to clinical risk parameters, for the early identification of patients that will subsequently deteriorate and/or have a higher risk of death.
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