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Table 1 Characteristics of the involved studies

From: The clinical value of cytokines in chronic fatigue syndrome

References Participants (n) Age (years) Course (years) Samples Findings
Moneghetti [45] CFS/ME P (24) 46.3 ± 10.9 NA B The most discriminatory cytokines between ME/CFS cases and controls post exercise were serum CD40L, PAI-1, IL1-β, IFN-α and CXCL1
HC (24) 41.6 ± 10.7
Milrad [26] CFS P (242) 49.36 ± 10.9 NA B Higher evening cortisol predicted greater depressive symptoms and circulating pro-inflammatory cytokines IL-2, IL-6, and TNF-α in CFS patients
HC (392) 50.1 ± 12.5
Clark [54] CFS P (24) 40. 3 ± 12.2 NA B Serum TGF-β increased in patients compared to controls at rest; no difference of cytokines IL-2, IL-4, IL-5, IL-10, IL-12, p70, and IFN-γ between cases and controls
HC (21) 39. 3 ± 14.1
Milrad [3] CFS/ME P (60) 50.52 ± 10.88 NA B Poor sleep quality is associated with enhancements of IL-1β, IL-6 and h fatigue severity
Montoya [22] CFS/ME P (192) 49.9 ± 12.7 NA B Cytokines CCL11, CXCL1, CXCL10, IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α had a statistically significant upward linear trend correlated with ME/CFS severity
Russell [37] Age ≤ 18 years ME/CFS P (18) 15.78 + 1.69 2.0 + 0.0 B Plasm IL-1α increased in recently ill adolescent ME/CFS subjects, and was progressively less important with duration; IL-8 increase screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years; IL-6 decrease suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years
18 < Age ≤ 50 years ME/CFS P (22) 40.82 + 6.17 7.1 + 6.0
Age > 50 years ME/CFS P (28) 60.21 + 6.66 10.6 + 7.7
HC (73) 14-60  
Hornig [80] CFS/ME P (32) 44.2 ± 7.1 7.6 ± 7.3 C Cytokines IL-1ra, IL-1β, IL-5, IL-6, IL-8, IL-10, IL-12p40, IL-17F, TNF-β, SCF, CSF1, CSF2, CSF3, PDGFBB, FGFb, VEGFA, LIF, resistin, serpin E1, sICAM1 and VCAM1 decreased; CCL11 and CXCL10 increased in CFS patients in comparison to no disease control
MS P (40) 49.9 ± 11.4
HC (19) 50.5 ± 8.5
Hornig [33] Short-duration ME/CFS P (52) 40.05 ± 13.6 1.7 ± 0.8 B Plasm IL-1α, CXCL8, IL-12p40, IL-17A, TNFα, sFasL, TRAIL, CCL2, SCF, resistin, IL-1RA and IL-13 increased; CD40L and PDGFBB decreased in short duration CFS patients versus long duration CFS patients and control
Long-duration ME/CFS P (246) 50.02 ± 11.4 15.6 ± 8.2
HC (348) 48.5 ± 12.0 Blank control
Peterson [79] CFS P (18) NA NA C IL-10 decreased in the CFS/ME patients in comparison to the controls
HC (15) NA
Hardcastle [34] Severely CFS/ME P (19) 40.21 + 1.57 13.071 + 6.639 B Serum IL-1β and RANTES decreased, IFN-γ increased in severe compared with moderate CFS/ME patients; IL-6 decreased in moderate CFS/ME patients compared with healthy controls and severe CFS/ME patients; IL-7and IL-8 increased in the severe CFS/ME group compared with healthy controls and moderate CFS/ME patients
Moderately CFS/ME P (22) 42.09 + 2.72 9.00 + 8.870
HC (22) 40.14 + 2.38
Maes [84] CF P (37) 41.6 ± 11.5 NA B Plasma IL-1 and TNF-α increased, serum neopterin increased in CFS and ME than in CF patients
CFS P (58) 39.1 ± 13.2
MEP (49) 43.7 ± 13.1
Brenu [50] CFS/ME P (65) 47.2 ± 11.5 16.4 ± 12.5 B Cytokines IL-10, IFN-γ and TNF-α increased at baseline; IL-10 and IL-17A decreased at 6 months; IL-2 increased at 12 months in the CFS/ME group in comparison to the non-fatigued controls
HC (21). 45.2 ± 9.3
Brenu [18] CFS/ME P (95) 46.47 ± 11.7 NA B CFS/ME patients displayed IL-10, IFN-γ and TNF-α enhancement in PBMCs
HC (50) 41.9 ± 9.6
Broderick [19] CFS P (40) 50 NA B Circulating level of IL-1a, 1b, IL- 4, IL- 5, IL- 6, IL- 12 and LTα increased; IL-8, IL-13, and IL-15 decreased; no difference of IL-2, 10, 17, IL-23, IFN-γ, and TNF-α was found in CFS patients compared with controls
HC (59) 53
Fletcher [43] CFS P (40) 50 NA B Plasma LTα, IL-1α, IL-1β, IL-4, IL-5, IL-6 and IL-12 increased, IL-8, IL-13 and IL-15 decreased, no difference of TNF-α, IFN-γ, IL-2, IL-10, IL-23 and IL-17 was found when comparing CFS with controls
HC (59) 53
Nater [36] CFS P (28) 49.6 NA B Changes of diurnal salivary cortisol rhythm were identical with IL-6 enhancement in CFS cases compared with the other groups
Persons with ISF (35) 49.2
ter Wolbeek [48] CFS P (11) 15.91 ± 1.34 0.62 ± 0.32 B Anti-inflammatory cytokines IL-10 increased (IFN-γ/IL-10 decreased), pro-inflammatory cytokines IL-6, and TNF-a decreased in CFS patients when compared with the severely fatigued or non-fatigued participants
Severely fatigued controls (67) 15.18 ± 1.37
Non-fatigued controls (61) 14.74 ± 1.60
Natelson [78] CFS P (44) 41.4 ± 8.0 NA C GM-CSF decreased in patients in comparison to the controls; IL-8 increased in patients with sudden, influenza-like onset than in patients with gradual onset or in controls; IL-10 increased in the patients with abnormal spinal fluids than in those with normal fluid or controls
HC (13) 33.0 ± 10.5
Zhang [52] Veterans CFS (43) 47.2 ± 11.5 NA B IL-2, IL-10, IFN-γ, and TNF-α increased in veterans with CFS compared with controls; there were no changes between civilians with CFS and controls
Veterans control (34) NA  
Civilian CFS (68) NA NA
Civilian control (53) NA  
Borish [49] CFS patients (18) 43.3 NA B TNF-α increase in PBMCs is observed in CFS group and allergic group but not in depression group compared with control group. IL-10 decrease in PBMCs in CFS group, allergic group and depression group compared with control group
HC (11) 42.9
Allergic control subjects (14) 43.3
Depression control subjects (12) 45.8
Vojdani [30] CFS P (29) 17–71 1–5 B IFN-α increased in patients with CSF in plasma and cell lysate
HC (15) 17–60
  1. B blood, C cerebrospinal fluid, PBMCs peripheral blood mononuclear cell, LTα lymphotoxin-alpha, GM-CSF granulocyte-macrophage colony-stimulating factor, PAI-1 plasminogen activator inhibitor, sFasL soluble Fas ligand, IL-1RA IL-1 receptor antagonist, CD40L CD40 ligand, MS multiple sclerosis, ISF insufficient symptoms or fatigue (for CFS diagnosis)