Brighton and Sussex Medical School, Falmer, East Sussex, BN1 9PS, United Kingdom.
Brighton and Sussex University Hospitals NHS Trust, Eastern Road, Brighton, BN2 5BE, United Kingdom.
Sci Rep. 2016 Jun 20;6:28006. doi: 10.1038/srep28006.
Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these 'circulating inflammation-related microRNAs' (CIR-miRNAs) were 2.64 (IQR: 2.10-3.29) and 1.52 (IQR: 1.15-1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742-0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets.
人类的全身炎症可能由感染引起，称为败血症，也可能由非感染性过程引起，称为非感染性全身炎症反应综合征（SIRS）。 microRNAs 调节包括炎症在内的细胞过程，并且可以在血液中检测到。我们旨在确立明确的原理证明，即在败血症和非感染性 SIRS 期间循环 microRNAs 会受到不同的影响。
患有严重（n=21）或非严重（n=8）腹腔内败血症的重症患者；严重（n=23）或非严重（n=21）非感染性 SIRS；或无 SIRS（n=16）的患者进行了研究。使用下一代测序和 qRT-PCR 测量血浆 microRNAs。与无 SIRS 患者相比，SIRS 患者通常检测到可检测的血液 miRNA（n=116）上调。这些“循环炎症相关 microRNAs”（CIR-miRNAs）的水平分别在非感染性 SIRS 和败血症中高 2.64（IQR：2.10-3.29）和 1.52（IQR：1.15-1.92）倍（p<0.0001），因此，败血症中 CIR-miRNAs 的丰度低于 SIRS。六种 CIR-miRNAs（miR-30d-5p、miR-30a-5p、miR-192-5p、miR-26a-5p、miR-23a-5p、miR-191-5p）可很好地区分严重败血症与严重 SIRS（ROC 曲线的 AUC 为 0.742-0.917）。CIR-miRNA 水平与促炎细胞因子（IL-1、IL-6 等）呈负相关。因此，在重症患者中，败血症和非感染性 SIRS 与 CIR-miRNA 的大量差异变化相关。CIR-miRNAs 可能是炎症的调节剂，值得作为诊断和治疗靶点进行深入评估。
