Table 1 Characteristics of the involved studies

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