Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Front Immunol. 2018 Apr 6;9:691. doi: 10.3389/fimmu.2018.00691. eCollection 2018.
Systemic levels of cytokines are altered during infection and sepsis. This prospective observational study aimed to investigate whether plasma levels of multiple inflammatory mediators differed between sepsis patients with and those without bacteremia during the initial phase of hospitalization. A total of 80 sepsis patients with proven bacterial infection and no immunosuppression were included in the study. Plasma samples were collected within 24 h of hospitalization, and Luminex analysis was performed on 35 mediators: 16 cytokines, six growth factors, four adhesion molecules, and nine matrix metalloproteases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs). Forty-two patients (52.5%) and 38 (47.5%) patients showed positive and negative blood cultures, respectively. There were significant differences in plasma levels of six soluble mediators between the two "bacteremia" and "non-bacteremia" groups, using Mann-Whitney test ( < 0.0014): tumor necrosis factor alpha (TNFα), CCL4, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and TIMP-1. Ten soluble mediators also significantly differed in plasma levels between the two groups, with -values ranging between 0.05 and 0.0014: interleukin (IL)-1ra, IL-10, CCL2, CCL5, CXCL8, CXCL11, hepatocyte growth factor, MMP-8, TIMP-2, and TIMP-4. VCAM-1 showed the most robust results using univariate and multivariate logistic regression. Using unsupervised hierarchical clustering, we found that TNFα, CCL4, E-selectin, VCAM-1, ICAM-1, and TIMP-1 could be used to discriminate between patients with and those without bacteremia. Patients with bacteremia were mainly clustered in two separate groups (two upper clusters, 41/42, 98%), with higher levels of the mediators. One (2%) patient with bacteremia was clustered in the lower cluster, which compromised most of the patients without bacteremia (23/38, 61%) (χ test, < 0.0001). Our study showed that analysis of the plasma inflammatory mediator profile could represent a potential strategy for early identification of patients with bacteremia.
在感染和脓毒症期间,细胞因子的全身水平会发生改变。本前瞻性观察研究旨在探讨在住院初期,是否有多种炎症介质的血浆水平在患有败血症且无菌血症和不伴菌血症的患者之间存在差异。本研究共纳入 80 例有明确细菌感染且无免疫抑制的败血症患者。采集患者入院后 24 小时内的血浆样本,采用 Luminex 分析法检测 35 种介质:16 种细胞因子、6 种生长因子、4 种黏附分子和 9 种基质金属蛋白酶(MMPs)/金属蛋白酶组织抑制剂(TIMPs)。42 例(52.5%)和 38 例(47.5%)患者血培养阳性和阴性。采用 Mann-Whitney U 检验,两组“菌血症”和“非菌血症”患者的六种可溶性介质的血浆水平存在显著差异( < 0.0014):肿瘤坏死因子-α(TNFα)、CCL4、E-选择素、血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)和 TIMP-1。两组间血浆水平差异也有统计学意义的十种可溶性介质,β 值在 0.05 到 0.0014 之间:白细胞介素(IL)-1ra、IL-10、CCL2、CCL5、CXCL8、CXCL11、肝细胞生长因子、MMP-8、TIMP-2 和 TIMP-4。使用单因素和多因素逻辑回归分析,VCAM-1 的结果最为显著。通过无监督层次聚类,我们发现 TNFα、CCL4、E-选择素、VCAM-1、ICAM-1 和 TIMP-1 可用于区分菌血症患者和非菌血症患者。菌血症患者主要聚类为两个单独的组(两个上簇,41/42,98%),这些组的介质水平较高。1 例(2%)菌血症患者聚类在下簇,该簇主要由大多数非菌血症患者(23/38,61%)组成(χ 检验, < 0.0001)。本研究表明,分析血浆炎症介质谱可能是早期识别菌血症患者的一种潜在策略。