Fletcher Mary Ann, Zeng Xiao Rong, Barnes Zachary, Levis Silvina, Klimas Nancy G
Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL, USA.
J Transl Med. 2009 Nov 12;7:96. doi: 10.1186/1479-5876-7-96.
Chronic Fatigue Syndrome (CFS) studies from our laboratory and others have described cytokine abnormalities. Other studies reported no difference between CFS and controls. However, methodologies varied widely and few studies measured more than 4 or 5 cytokines. Multiplex technology permits the determination of cytokines for a large panel of cytokines simultaneously with high sensitivity and with only 30 ul of plasma per sample. No widely accepted laboratory test or marker is available for the diagnosis or prognosis of CFS. This study screened plasma factors to identify circulating biomarkers associated with CFS.
Cytokines were measured in plasma from female CFS cases and female healthy controls. Multiplex technology provided profiles of 16 plasma factors including the pro -inflammatory cytokines: tumor necrosis factor alpha (TNFalpha), lymphotoxin alpha (LTalpha), interleukin (IL) - IL-Ialpha, IL-1beta, IL-6; TH1 cytokines: interferon gamma (IFNgamma), IL-12p70, IL-2, IL-15; TH2: IL-4, IL-5; TH17 cytokines, IL-17 and IL-23; anti-inflammatory cytokines IL-10, IL-13; the inflammatory mediator and neutrophil attracting chemokine IL-8 (CXCL8). Analysis by receiver operating characteristic (ROC) curve assessed the biomarker potential of each cytokine.
The following cytokines were elevated in CFS compared to controls: LTalpha, IL-1alpha, IL-1beta, IL-4, IL-5, IL-6 and IL-12. The following cytokines were decreased in CFS: IL-8, IL-13 and IL-15. The following cytokines were not different: TNFalpha, IFNgamma, IL-2, IL-10, IL-23 and IL-17. Applying (ROC) curve analyses, areas under the curves (AUC) for IL-5 (0. 84), LTalpha (0.77), IL-4 (0.77), IL-12 (0.76) indicated good biomarker potential. The AUC of IL-6 (0.73), IL-15 (0.73), IL-8 (0.69), IL-13 (0.68) IL-1alpha (0.62), IL-1beta (0.62) showed fair potential as biomarkers.
Cytokine abnormalities are common in CFS. In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers. However, the cytokine changes observed are likely to more indicative of immune activation and inflammation, rather than specific for CFS. As such, they are targets for herapeutic strategies. Newer techniques allow evaluation of large panels of cytokines in a cost effective fashion.
我们实验室及其他机构对慢性疲劳综合征（CFS）的研究均描述了细胞因子异常情况。其他研究则报告称CFS与对照组之间并无差异。然而，研究方法差异很大，很少有研究检测超过4种或5种细胞因子。多重检测技术能够同时高灵敏度地测定大量细胞因子，每个样本仅需30微升血浆。目前尚无广泛认可的实验室检测方法或标志物可用于CFS的诊断或预后评估。本研究对血浆因子进行筛查，以确定与CFS相关的循环生物标志物。
检测女性CFS患者和女性健康对照者血浆中的细胞因子。多重检测技术提供了16种血浆因子的谱图，包括促炎细胞因子：肿瘤坏死因子α（TNFα）、淋巴毒素α（LTα）、白细胞介素（IL）-IL-1α、IL-1β、IL-6；TH1细胞因子：干扰素γ（IFNγ）、IL-12p70、IL-2、IL-15；TH2细胞因子：IL-4、IL-5；TH17细胞因子IL-17和IL-23；抗炎细胞因子IL-10、IL-13；炎症介质及嗜中性粒细胞趋化因子IL-8（CXCL8）。通过受试者工作特征（ROC）曲线分析评估每种细胞因子作为生物标志物的潜力。
与对照组相比，CFS患者中以下细胞因子水平升高：LTα、IL-1α、IL-1β、IL-4、IL-5、IL-6和IL-12。CFS患者中以下细胞因子水平降低：IL-8、IL-13和IL-15。以下细胞因子无差异：TNFα、IFNγ、IL-2、IL-10、IL-23和IL-17。应用ROC曲线分析，IL-5（0.84）、LTα（0.77）、IL-4（0.77）、IL-12（0.76）的曲线下面积（AUC）表明其具有良好的生物标志物潜力。IL-6（0.73）、IL-15（0.73）、IL-8（0.69）、IL-13（0.68）、IL-1α（0.62）、IL-1β（0.62）的AUC显示其作为生物标志物的潜力一般。
细胞因子异常在CFS中很常见。在本研究中，所检测的16种细胞因子中有10种显示出作为生物标志物的良好至一般前景。然而，观察到的细胞因子变化可能更多地指示免疫激活和炎症，而非CFS所特有。因此，它们是治疗策略的靶点。新技术能够以经济有效的方式评估大量细胞因子。
