Background
Methods
Setting
Searches
Inclusion and exclusion criteria
Data extraction
Quality assessment
Level | Differential diagnosis/symptom prevalence study | Blinded | Controls | Remark/example |
---|---|---|---|---|
1a | Systematic review of prospective cohort studies | NR | NR | No systematic reviews available |
1b | Prospective cohort study with good follow-up | NR | Implicit | An item is assessed (e.g. breast implant) and the occurrence of FMS is followed prospectively |
1c | All or none case series | Test and assessment of results | Obligatory | All patients with low IL-4 have FMS, none has high IL-4 |
1d | 1c | Test or assessment of results | Obligatory | 1c |
2a | Systematic review (with homogeneity) of | NR | NR | No systematic reviews available |
2b and better studies | ||||
2b | Retrospective cohort study, or poor follow-up | NR | Implicit | FMS patients are investigated now, if they have had breast implants in the past; large size studies |
2c | Ecological studies | Test and assessment of results | Implicit | FMS patients are investigated simultaneously, if they have FMS and if they have low IL-4 levels. |
2d | 2c | Test or assessment of results | Implicit | 2c |
3a | Systematic review (with homogeneity) of 3b and better studies | No systematic reviews available | ||
3b | Non-consecutive cohort study, or very limited population | Test and assessment of results | Obligatory | FMS patients and controls (limited population) are now investigated if they have low IL-4 |
levels | ||||
3c | 3b | Test or assessment of results | Obligatory | 3b |
3d | 1c, 2c, 3b | Not blinded | Obligatory | |
4 | Case series or superseded reference standards | All studies without control group | Case series with historical controls; case reports | |
5 | Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles" | NR |
Item | |
---|---|
1 | Standardized method OR citation OR new method with adequate description including 2-5? |
2 | Adequate description of the method itself? |
3 | Sensitivity limits of the method declared? |
4 | Adequate internal controls measured? |
5 | Adequate negative controls measured? |
6 | Adequate number of samples investigated? |
7 | Adequate comparison with the control group? |
8 | All reagent information given? |
9 | Time points of tissue/blood collection standardized and given? |
10 | Measurements or data assessment performed in a blinded manner? |
11 | Adequate data assessment and illustration? |
12 | Target of interest investigated with > 1 method? |
Data synthesis and analysis
Results
Study selection
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 |
Majority of studies with low quality
High variability of materials and methods
Systematic review
Serum (Table 4)
Author, yr. Diagnosis criteria | N patients/controls | a) Material b) Methods c) Investigated targets | Results | Modified CEBM level | NOS | W-MeQS |
---|---|---|---|---|---|---|
Maes, 1999 ACR | 21/33 | a) serum B) ELISA c) IL-6, sIL-6 R, sIL-1R, IL-1 RA | In FMS compared to controls: IL-6↔ sIL-6 R ⇑ sIL-1R ⇑ IL-1 RA ⇑ | 3d | 2 | 0.3 |
Pay. 2000 ACR | 25 FMS/25 chronic musculoskeletal complaints/25 controls | a) serum b) ELISA c) IL-1b, TNF, IL-6 | No difference for pro-inflammatory cytokines in FMS and controls. | 3d | 3 | 0.4 |
Wallace, 2001 ACR | 56/56 | a) serum, PBMC, plasma b) ELISA c) IL-1β, IL-2, IL-6, IL-8, IL-10, sIL-2 R, IL-1 RA, IFNγ, TNF | In FMS compared to controls: IL-1β, IL-2, IL-6, IL-8, IL-10, sIL-2 R, IFNγ, TNF: ↔ in sera +PBMC IL-1 RA: ⇑ 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 |
Ardic, 2006 ACR | 21/10 (data not given) | 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, TNF | No intergroup difference for cytokines. | 3d | 3 | 0.2 |
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 |
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-1b, IL-1Ra, IL-4, IL-6, IL-8, IL-10, INFγ, TNF | FMS > controls: IL-1Ra, IL-6, IL-10, TNF | 3d | 3 | 0.7 |
Ross, 2010 ACR | 24/none | a) serum b) bead-based immunofluorescence assay c) IL-1a, IL-1b, 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-1a vice versa. | 4 | 1 | 0.2 |
Plasma (Table 5)
Author, yr. Diagnosis criteria | N patients/controls | a) Material b) Methods c) Investigated targets | Results | Modified CEBM level | NOS | W-MeQS |
---|---|---|---|---|---|---|
Wallace, 2001 ACR | 56/56 | 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-1RA, IL-6: ⇑ in PBMC IL-6: ⇑ in PBMC of patients with disease duration > 2 years. | 3d | 3 | 0.5 |
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, TNF | 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 |
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. | 3d | 2 | 0.8 |
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-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-12, IL-15, IL-17, TNF, IFNα, IFNγ, GM-CSF, MIG, MIP-1α, MIP-1β, 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-1α, 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 | 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 |
Whole blood (Table 6)
Author, yr. Diagnosis criteria | N patients/controls | a) Material b) Methods c) Investigated targets | Results | Modified CEBM level | NOS | W-MeQS |
---|---|---|---|---|---|---|
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 |
Peripheral blood mononuclear cells (Table 7)
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 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 cite Wolfe, 1985 | 12 FMS/6 rheumatoid arthritis or osteoarthritis controls/6 | a) supernatant of PBMC b) in vitro stimulation of PBMC with different L-tryptophan, contaminated L-tryptophan, peak E; self established double sandwich ELISA c) IL-4, IL-2, INF-γ, 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 |
Wallace, 2001 ACR | 56/56 | a) serum, PBMC b) ELISA c) IL-1β, IL-2, IL-6, IL-8, IL-10, sIL-2 R, IL-1 RA, IFNγ, TNF | In FMS compared to controls: IL-1β, IL-2, IL-10, sIL-2 R, IFNγ, TNF: ↔ in sera + PBMC IL-1 RA, IL-8: ⇑ in sera IL-1 RA, IL-6: ⇑ in PBMC IL-6: ⇑ in PBMC of patients with disease duration > 2 years. | 3d | 3 | 0.5 |
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 |
Kaufmann, 2007 ACR | 22/15 CRPS/37 | a) T-cells b) FACS analysis c) IL-2, IFN-γ, IL-4, IL-10 | No difference in percentage of cytokine producing cells between FMS and controls. | 3d | 2 | 0.6 |
Macedo, 2007 ACR | 18/22 | a) blood, 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, IFN-γ, TNF | After dexamethasone: reduction of cytokines FMS > controls. | 3d | 2 | 0.4 |
Ortega, 2010 ACR | 9/9 | a) PBMC b) ELISA c) IL-1b, 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 |
Skin (Table 8)
Author, yr. Diagnosis criteria | N patients/controls | a) Material b) Methods c) Investigated targets | Results | Modified CEBM level | NOS | W-MeQS |
---|---|---|---|---|---|---|
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 |
Blanco, 2010 ACR | 63/49 | a) skin b) IHC c) MCP-1, TNF | MCP-1: FMS < controls | 3c | 3 | 0.8 |
Meta-analysis
Study | FMS | Controls | Weight | SMD | ||||
---|---|---|---|---|---|---|---|---|
Mean | Std | Total | Mean | Std | Total | IV, Random, 95% CI | ||
IL-1: plasma, ELISA or immunoassay
| ||||||||
Togo 2009 | 0.79 | 0.64 | 7 | 1.24 | 1.17 | 9 | 16.4% | -0.43 [-1.44, 0.57] |
Feng 2009 | 74.5 | 116.5 | 100 | 45.6 | 53.1 | 35 | 41.3% | 0.28 [-0.11, 0.66] |
Bazzichi 2007 | 4.54 | 9.7 | 80 | 7.44 | 6.62 | 45 | 42.3% | -0.33 [-0.70, 0.04] |
Total (95% CI) | 187 | 89 | 100.0% | -0.10 [-0.58, 0.39] | ||||
Heterogeneity: Tau2 = 0.11; Chi2 = 5.52, df = 2 (P = 0.06); I2 = 64% | ||||||||
Test for overall effect: Z = 0.39 (P = 0.69) | ||||||||
IL-6: plasma, ELISA or immunoassay or bioplex assay
| ||||||||
Togo 2009 | 14.0 | 10.9 | 7 | 16.8 | 15.3 | 9 | 9.6% | -0.19 [-1.19, 0.80] |
Schwarz 2002 | 1.01 | 0.47 | 17 | 1.45 | 2.17 | 17 | 20.7% | -0.27 [-0.95, 0.40] |
Bazzichi 2007 | 2.76 | 3.99 | 80 | 4.34 | 4.51 | 45 | 69.7% | -0.38 [-0.74, -0.01] |
Total (95% CI) | 104 | 71 | 100.0% | -0.34 [-0.64, -0.03] | ||||
Heterogeneity: Tau2 = 0.00; Chi2 = 0.15, df = 2 (P = 0.93); I2 = 0% | ||||||||
Test for overall effect: Z = 2.15 (P = 0.03) | ||||||||
IL-6: serum, ELISA or immunoassay or bioplex assay
| ||||||||
Gür 2002 | 5.52 | 3.96 | 81 | 5.46 | 1.37 | 32 | 25.7% | 0.02 [-0.39, 0.43] |
Hernandez 2010 | 16.28 | 8.13 | 64 | 0.92 | 0.32 | 25 | 24.8% | 2.20 [1.63, 2.77] |
Wallace 2001 | 7.19 | 2.02 | 56 | 6.3 | 6.72 | 36 | 25.6% | 0.20 [-0.22, 0.62] |
Wang 2008 | 2.57 | 1.38 | 20 | 0.92 | 0.32 | 25 | 23.9% | 1.71 [1.02, 2.40] |
Total (95% CI) | 221 | 118 | 100.0% | 1.01 [-0.03, 2.05] | ||||
Heterogeneity: Tau2 = 1.05; Chi2 = 51.09, df = 3 (P < 0.00001); I2 = 94% | ||||||||
Test for overall effect: Z = 1.91 (P = 0.06) | ||||||||
IL-8: plasma, ELISA or immunoassay
| ||||||||
Bazzichi 2007 | 61.89 | 149.0 | 80 | 7.9 | 17.5 | 45 | 41.2% | 0.45 [0.08, 0.82] |
Blanco 2010 | 83.0 | 253.0 | 79 | 84.0 | 253.0 | 59 | 42.8% | -0.00 [-0.34, 0.33] |
Togo 2009 | 8.4 | 1.9 | 7 | 11.8 | 5.4 | 9 | 16.0% | -0.75 [-1.79, 0.28] |
Total (95% CI) | 166 | 113 | 100.0% | 0.06 [-0.43, 0.56] | ||||
Heterogeneity: Tau2 = 0.12; Chi2 = 6.23, df = 2 (P = 0.04); I2 = 68% | ||||||||
Test for overall effect: Z = 0.25 (P = 0.80) | ||||||||
TNF: serum, ELISA or immunoassay or bioplex assay
| ||||||||
Hernandez 2010 | 20.42 | 7.24 | 64 | 35.73 | 0.72 | 25 | 33.0% | -2.46 [-3.05, -1.87] |
Wang 2008 | 3.27 | 5.08 | 20 | 3.89 | 12.95 | 80 | 33.5% | -0.05 [-0.54, 0.44] |
Üçeyler 2006 | 7.41 | 11.01 | 26 | 6.7 | 9.5 | 40 | 33.5% | 0.07 [-0.42, 0.56] |
Total (95% CI) | 110 | 145 | 100.0% | -0.81 [-2.31, 0.70] | ||||
Heterogeneity: Tau2 = 1.70; Chi2 = 49.74, df = 2 (P < 0.00001); I2 = 96% | ||||||||
Test for overall effect: Z = 1.05 (P = 0.29) | ||||||||
TNF: plasma, ELISA or immunoassay
| ||||||||
Bazzichi 2007 | 22.59 | 29.55 | 80 | 11.07 | 6.77 | 45 | 28.0% | 0.48 [0.11, 0.85] |
Blanco 2010 | 163.0 | 435.0 | 79 | 161.0 | 319.0 | 59 | 28.5% | 0.01 [-0.33, 0.34] |
Feng 2009 | 12.2 | 10.2 | 100 | 40.1 | 73.5 | 35 | 27.6% | -0.73 [-1.12, -0.33] |
Togo 2009 | 0.24 | 0.13 | 7 | 0.7 | 0.61 | 9 | 16.0% | -0.93 [-1.98, 0.13] |
Total (95% CI) | 266 | 148 | 100.0% | -0.21 [-0.82, 0.39] | ||||
Heterogeneity: Tau2 = 0.30; Chi2 = 21.71, df = 3 (P < 0.0001); I2 = 86% | ||||||||
Test for overall effect: Z = 0.69 (P = 0.49) |