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Table 3 Characteristics of all studies included in the systematic review investigating cytokines in FMS patients.

From: Systematic review with meta-analysis: cytokines in fibromyalgia syndrome

Author, yr.
Diagnosis criteria
N patients/controls a) Material
b) Methods
c) Investigated targets
Results Modified CEBM
level
NOS W-MeQS
Hader, 1991
Smythe
12/10 a) CD4+ T-lymphocytes from PBMC
b) T-cell culture; stimulation experiments with mitogens and measurement of IL-2 secretion
c) IL-2
FMS: higher concentration of mitogen was necessary to achieve optimal IL-2 secretion; peak time of IL-2 secretion was delayed.
Addition of calcium did not correct the reduction in IL-2 secretion in patients with FMS; addition of phorbole myristate acetate led to normal IL-2 secretion.
3d 2 0.4
Barth, 1999
Wolfe, 1985
12 FMS/6 rheumatoid arthritis or osteoarthritis controls/6 controls a) supernatant of PBMC
b) self established double sandwich ELISA;
c) IL-4; IL-2; INFγ; GM-CSF; IL-5, IL-10
In vitro stimulation of PBMC with different L-tryptophan preparations: 6/12 FMS patients, 2/12 controls: IL-5 and IL-10 production 3d 4 0.1
Maes, 1999
ACR
21/33 a) serum
B) ELISA
c) IL-6, sIL-6 R, sIL-1R, IL-1RA
In FMS compared to controls:
IL-6↔
sIL-6R
sIL-1R
IL-1RA
3d 2 0.3
Pay. 2000
ACR
25 FMS/25 chronic musculoskeletal complaints/25 controls a) serum
b) ELISA
c) IL-1β, TNF, IL-6
No difference for pro-inflammatory cytokines in FMS and controls. 3d 3 0.4
Wallace, 2001
ACR
56/56
Serum, PBMC
a) serum, PBMC, plasma
b) ELISA
c) IL-1β, IL-2, IL-6, IL-8, IL-10, sIL-2R, IL-1RA, IFNγ, TNF
In FMS compared to controls:
IL-1β, IL-2, IL-6, IL-8, IL-10, sIL-2R, IFNγ, TNF: ↔ in sera +PBMC
IL-1RA: in serum
IL-8: in plasma IL-1 RA, IL-6: in PBMC
IL-6: in PBMC of patients with disease duration > 2 years.
3d 3 0.5
Gür, 2002
ACR
81/32 a) serum
b) ELISA
c) IL-1, IL-2R, IL-6, IL-8
In FMS compared to controls:
IL-1 ↔
IL-2 R
IL-6 ↔
IL-8
3d 2 0.4
Schwarz, 2002
ACR
17/17 a) serum
b) ELISA
c) IL-6
IL-6 during tryptophan depletion in FMS 3d 4 0.3
Amel Kashipaz, 2003
ACR
22 FMS/CFS/19 a) PBMC
b) intracellular cytokine stain; flow cytometry
c) IL-1α, IL-6, IL-10, TNF
In FMS compared to controls:
IL-1α ↔
IL-6 ↔
IL-10 ↔
TNF ↔
3d 2 0.7
Salemi, 2003
ACR
53/10 a) skin biopsy
b) RT-PCR, IHC
c) IL-1β, IL-6, TNF
Detectable cytokines in FMS:
IL-1β (19/50)
IL-6 (14/51)
TNF (17/53)
None of the cytokines could be detected in control skin.
3d 2 0.7
Ardic, 2006
ACR
21/10 a) serum
b) ELISA
c) IL-1 (after balneo therapy)
After balneo therapy:
IL-1↓ in FMS
3d 3 0.2
Üçeyler, 2006
ACR
26/40 a) serum; whole blood
b) qRT-PCR;
ELISA
c) IL-2, IL-4, IL-8, IL-10, TNF, TGF-β1
In FMS compared to controls:
IL-2 ↔
IL-4
IL-8 ↔
IL-10
TGF-β1 ↔
TNF ↔
3d 4 0.8
Bazzichi, 2007
ACR
285/40 (16 rheumatoid arthritis cases, two Sjögren's syndrome cases, 16 systemic lupus erythematosus cases,
four systemic sclerosis cases, two undifferentiated connective-
tissue disease cases)/100
a) serum, plasma
b) ELISA
c) IL-1, IL-6, IL-8, IL-10, TNFα
No intergroup difference for cytokines. 3d 3 0.2
Bazzichi, 2007
ACR
80/45 a) plasma
b) ELISA
c) IL-1, IL-6, IL-8, IL-10, TNF
IL-10, IL-8, TNF: FMS > controls 3c 3 0.9
Macedo, 2007
ACR
18/22 a) PBMC
b) automated biochip array; before and after 1.5 mg of dexamethasone per os
c) IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IFNγ, TNF
After dexamethasone: reduction of cytokines FMS > controls. 3d 2 0.4
Kaufmann, 2007
ACR
22/15 CRPS/37 a) T-cells
b) FACS analysis
c) IL-2, IFNγ, IL-4, IL-10
No difference in percentage of cytokine producing cells between FMS and controls. 3d 2 0.6
Togo,
2008
ACR
7/9 a) plasma
b) Beadlyte multi-cytokine assay
c) IL-10, IL-6, IL-8, IL-1, TNF
No difference between groups.
"FM patients showed a shift to increased IL-10 in the
nighttime compared to controls."
3d 2 0.8
Wang, 2008
ACR
20/80 a) serum
b) Bio-Plex cytokine assay
c) IL-6, IL-8, IL-10, IL-4, TNF
At baseline: IL-8 in FMS > controls; no difference for other cytokines. 3d 4 0.4
Zhang, 2008
ACR
92/69 family members/62 anonymous blood samples from blood bank a) plasma
b) Cytokine Twenty-Five-Plex Antibody Bead Kit
c) MCP-1, Eotaxin, IP-10, IL-13, IL-5, IL-10, IL-1b, IL-2, IL-4, IL-6, IL-7, IL-8, IL-12, IL-15, IL-17, TNF, IFNa, IFNg, GM-CSF, MIG, MIP-1a, MIP-1b, IL-1ra, IL-2r
Eotaxin and MIP: FMS > controls 3d 3 0.5
Feng, 2009
ACR
100 FMS patients and family members/35 unaffected parents a) plasma
b) Cytokine Twenty-Five-Plex Antibody Bead Kit
c) Eotaxin, MIP.1a, MCP-1, IP10, IL-12, IL-1β
Rare missense variants of the MEFV gene are associated with risk of FMS and are present in a subset of 15% of FMS patients. This subset had, on average, high levels of plasma IL-1b compared to FMS patients without rare variants, unaffected family members with or without rare variants, and unrelated controls of unknown genotype. 3d 3 0.4
Blanco, 2010
ACR
63/49 a) skin
b) immuno-histochemistry
c) MCP-1, TNF
MCP-1: FMS < controls 3c 3 0.8
Blanco, 2010
ACR
79/59 a) plasma
b) sandwich enzyme immunoassay kits
c) IL-8, TNF, sTNF-RI, sTNF-RII, MCP-1
Patients with FMS have lower systemic levels of MCP-2 than controls. 3d 3 0.4
Hernandez, 2010
ACR
64/25 a) serum
b) ELISA
c) TNF, IL-1, IL-6
TNF: FMS < controls
IL-1: not detectable in FMS
IL-6: FMS > controls
3c 4 0.6
Iannucelli, 2010
ACR
51/25 tension type headache/15 a) serum
b) multiplex bead-based sandwich immunoassay
c) IL-1β, IL-1Rα, IL-4, IL-6, IL-8, IL-10, INFγ, TNF
FMS > controls: IL-1RA, IL-6, IL-10, TNF 3d 3 0.7
Ortega, 2010
ACR
9/9 a) PBMC
b) ELISA
c) IL-1β, TNF, IL-6, IL-10
For all cytokines investigated: higher values at baseline in FMS compared to controls; after aquatic exercise levels as in controls. 3d 3 0.3
Ross, 2010
ACR
24/none a) serum
b) bead-based immunofluorescence assay
c) IL-1α, IL-1β, IL-1RA, IL-6, IL-8, IL-10, TNF
IL-6 and IL-8: FMS responders (i.e. GH response to exercise of ≥ 5 ng/mL) higher than FMS non-responders. For IL-1α vice versa. 4 1 0.2
  1. Abbreviations:
  2. ACR: American College of Rheumatology; CEMB: Center of Evidence Based Medicine; ELISA: enzyme linked immunosorbent assay; FMS: fibromyalgia syndrome; IL: interleukin; NOS: Newcastle Ottawa Scale; NR: not reported; PBMC: peripheral blood mononuclear cells; qRT-PCR: quantitative real-time PCR; R: receptor; RA: receptor antagonist; W-MeQS: Würzburg Methodological Quality Score; yrs: years
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