title: Plasma cytokines in women with chronic fatigue syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL, USA. mfletche@med.miami.edu
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Fletcher
authors.forename: Xiao Rong
authors.initials: XR
authors.lastname: Zeng
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barnes
authors.forename: Silvina
authors.initials: S
authors.lastname: Levis
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Klimas
mesh_terms: D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D046228:Microarray Analysis; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D016207:Cytokines