In the original article, there was a mistake in Appendix Table A1, Cytokine studies of ME/CFS as published. In the “Montoya et al. (2017)” row, the words “and plasma” should have been removed from the “Sample matrix” column as only the serum was analyzed. The words “kit not specified” from the “Kits” column should also be removed. The specific model/catalog number of their 51-multiplex array was not specified, but the table's wording could be misinterpreted because Montoya et al. (2017) specified other assay details.
Table A1.
Cytokine studies of ME/CFS.
| Study | Diagnostic criteria | Sample handling and processing | Assays | Assay results | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample matrix | Collection (Specifications of note) | Time of collection | Storage | Method | Manufacturer | Kits | Increase | Decrease | No difference | ||
| Lynn et al. 2018 (109) | Fukuda et al. 1994 (71) | Plasma | samples taken at 30 min intervals on two consecutive days | 10:00 a.m.−12:00 p.m. | −80°C | Multiplex | BD Biosciences | Human CBA kit | IL-6, TNFα (response to low dose dex, LPS) | IP-10, IL-12/23p40 | |
| Richardson et al. 2018 (110) | Carruthers et al. 2003 (223) | Serum | non-fasting blood samples collected after 20-min standing test | – | – | Both | BD Biosciences; activin ELISA supplied by Oxford Brookes University | Human CBA kit 560484 | serum activin B | IL-2, IL-4, IL-6, IL-10, TNF, IFN γ, IL-17A, activin A | |
| Oka et al. 2018 (111) | Fukuda et al. 1994 (71), Carruthers et al. 2011 (225), and SEID, 2015 (230) | Serum and plasma (TGF-β1, BDNF) | after 8 weeks of intervention, blood sampling before and after the last session | 2:00–4:00 p.m. | −80°C | ELISA | Fujirebio, R&D, pbl assay science, BioSource Europe S.A.; R&D | IL-6 CLEIA cartridge; Quantikine high-sensitivity ELISA human TNF-α immunoassay; VeriKine Human Interferon Alpha Multi-Subtype Serum ELISA kit; MEDGENIX human IFNγ EASIA kit; Quantikine; Quantikine ELISA human TGF-β1 kit, BDNF kit | TNF-α | IL-6; IFN-α, IFN-γ; TGF-β1, BDNF | |
| Moneghetti et al. 2018 (112) | Fukuda et al. 1994 (71) and Carruthers et al. 2011 (225) for PEM | Serum | fasting blood sample | morning | −80°C | Multiplex | Affymetrix | 51-Plex Luminex bead kit | CXCL 10 | IL-8, CXCL10, CCL4, TNF-β, ICAM-1 | IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL12p40, IL12p70, IL-13, IL-15, IL-17, IL-17F, IL-18, LIF |
| Milrad et al. 2018 (115) | Fukuda et al. 1994 (71) | Plasma | – | 11:00 a.m.−3:00 p.m. | −80°C | Multiplex | Quansys (R&D) | Q-plex Human cytokine screen | IL-2, IL-6, TNF-α | ||
| Wyller et al. 2017 (113) | Fukuda et al. 1994 (71) and Carruthers et al. 2003 (223) | Plasma | fasting blood sample, no tobacco | 7:30–9:30 a.m. | −80°C | Multiplex | Bio-Rad Laboratories | Bio-Plex Human TGF-β 3-Plex | TGF-β1, TGF-β2, TGF-β3 | ||
| Roerink et al. 2017 (114) | Fukuda et al. 1994 (71) and Carruthers et al. 2003 (223) | Plasma | before and after 4 weeks of treatment | – | −80°C | Multiplex | Olink Proteomics AB; R&D | Proseek Multiplex Inflammation panel; TGF-β duo-set DY240 | Positively associated with risk of being an ME/CFS patient: CCL4, 1L12β, CCL11, FGF5, IL6, CCL23, CX3CL1, IL10, CXCL5 | Negatively associated with risk of being an ME/CFS patient: CXCL6, CXCL10, CXCL9, CCL28, CCL25, CCL20, CCL19, TRAIL, TNFβ, FGF23 | IFN-γ, IL-1α, IL-2, IL-4, IL17A, TNF, MCP-3, IL-17c, TSLP, PD-L1, IL-24, IL-13, IL-20, IL-33, LIF, IL-5 |
| Montoya et al. 2017 (116) | Fukuda et al. 1994 (71) | Serum | – | 8:30 a.m.−3:30 p.m. | −80°C | Multiplex | Affymetrix | 51-multiplex array | TGF-β; IL-13 in severe group (when stratified by severity); significant upward linear trend across severity: CCL11, CXCL1, CXCL10, G-CSF, GM-CSF, IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, LIF, NGF, SCF, TGF-α | resistin; significant nonlinear inverted trend: ICAM1, resistin | 34 others from 51-multiplex array |
| Nagy-Szakal et al. 2017 (117) | Fukuda et al. 1994 (71) and Carruthers et al. 2003 (223) | Plasma | – | – | −80°C | Multiplex | Affymetrix | Customized Procarta immunoassay (61-plex) | IL1α, IL1β, IL1RA, IL18, IL2, IL4, IL7, IL9, IL13, IL15, IL5, IL6, LIF, IL31, IL10, IL21, IL22, IL12p40, IL12p70, IL23, IL27, IL17A, IL17F, IFNα2, IFNβ, IFNγ, TNFα (TNFSF2), TNFβ (TNFSF1), sFasL (TNFSF6), TRAIL (TNFSF10), CCL2 (MCP1), CCL3 (MIP1a), CCL4 (MIP1b), CCL5 (RANTES), CCL7 (MCP3), CCL11 (eotaxin), CXCL1 (GROa), CXCL8 (IL8), CXCL9 (MIG), CXCL10 (IP10), CXCL12a (SDF1a), PDGFBB, VEGFA, VEGFD, sICAM1 (CD54), VCAM1 (CD106), serpin E1 (PAI1), leptin, resistin, TGFα, TGFβ, FGFβ, βNGF, HGF, SCF, MCSF (CSF1), GMCSF(CSF2), GCSF (CSF3), PlGF1, EGF, BDNF | ||
| Hornig et al. 2017 (118) | Fukuda et al. 1994 (71) and /or Carruthers et al. 2003 (223) | CSF | CSF samples from biobank | – | −80°C | Multiplex | Affymetrix | Customized Procarta immunoassay (51-plex) | FGFb in Classical-ME/CFS-short duration compared to Atypical-ME/CFS-short duration; SCF in Atypical-ME/CFS compared to Classical-ME/CFS irrespective of illness duration | IL1β, IL5, IL7, IL13, IL17A, IFNα2, IFNγ, TNFα, TRAIL (TNFSF10), CCL2, CCL7, CXCL5, CXCL9, CSF3 (GCSF), βNGF, resistin, serpin E1 (PAI1) in Atypical-ME/CFS-short duration compared to Classical-ME/CFS-short duration; IL7, IL17, CXCL9, serpin E1 in Atypical-ME/CFS-short duration compared to Classical-ME/CFS-long duration; IL5, IL13, IL17, CXCL9, in Atypical-ME/CFS-long duration compared to Classical-ME/CFS-short duration; IL6, IL17 in Atypical-ME/CFS-long duration compared to Classical-ME/CFS-long duration | IL1ra, IL1α, IL2, IL4, CXCL8 (IL8), IL10, IL12p40, IL12p70, IL15, IL17F, TNFβ, CD40L, sFasL, CCL3 (MIP1α), CCL4 (MIP1β), CCL5 (RANTES), CCL11 (eotaxin), CXCL1 (GROα), CXCL10 (IP10), TGFα, TGFβ, CSF1 (MCSF), CSF2 (GMCSF), PDGFBB, HGF, VEGFA, LIF, leptin, sICAM1 (CD54), VCAM1 (CD106) |
| Hanevik et al. 2017 (119) | Fukuda et al. 1994 (71) | PBMC | fasting blood samples | 8:00–9:00 a.m. | −80°C | Multiplex | Bio-Rad Laboratories | Bioplex assays, kits not specified | sCD40L in Giardia-exposed vs. unexposed ME/CFS subjects, and in post-infective-ME/CFS vs. no post-infective fatigue group | IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-22, MIP-1α, MIP-1β, TGFβ1, TGFβ2, TGFβ3, GM-CSF | |
| Lidbury et al. 2017 (120) | Carruthers et al. 2003 (223) | Serum | non-fasting samples collected after 20-min standing test | – | – | Both | BD Biosciences; activin kit supplied by Oxford Brookes University | Human CBA kit 560484 | Activin B | IL-2, IL-4, IL-6, IL-10, IL-17A, TNF, IFN-α, activin A, follistatin | |
| Milrad et al. 2017 (121) | Fukuda et al. 1994 (71) | Plasma | x | 11:00 a.m.−3:00 p.m. | −80°C | ELISA | Quansys Biosciences | Q-plex Human cytokine screen | IL-1β, IL-6, TNF-a within CFS patients associated with poor sleep quality in ME/CFS | ||
| Lunde et al. 2016 (122) | Fukuda et al. 1994 (71) and Carruthers et al. 2003 (223) | Serum and plasma | x | – | −80°C | ELISA | R&D; Invitrogen/Life technologies | BAFF and APRIL kits | BAFF in intervention group relative to baseline | APRIL | |
| Huth et al. 2016 (123) | Fukuda et al. 1994 (71) | PBMC | x | 7:30–10:00 a.m. | – | Neither | BD Biosciences; Biolegend | intracellular staining of stimulated and unstimulated PBMC cultures | IFN-γ, TNF-α and GM-CSF increased in culture after challenge, but no difference between groups | ||
| Russell et al. 2016 (124) | Jason et al. 2006 (226) and Fukuda et al. 1994 (71) and ICD | Plasma | fasting blood sample | morning | −80°C | ELISA | Quansys Biosciences | Q-plex Human cytokine screen (16-plex) | IL-4, IL-5, IL-12, LTα in ME/CFS patients relative to healthy controls; IL-8 in ME/CFS adolescents | IL-8, IL-15 ME/CFS patients relative to healthy controls; IL-23 in ME/CFS adolescents | IL-1α, IL-1β, IL-2, IL-6, IL-10, IL-13, IL-17, IFNγ, TNFα |
| Landi et al. 2016 (125) | Fukuda et al. 1994 (71) and Carruthers et al. 2003 (223) | Plasma | samples from Solve ME/CFS BioBank | – | −80°C | ELISA | Meso Scale Discovery | MSD Human V-PLEX Plus Kits: Chemokine Panel 1, Cytokine Panel 1, and Pro-inflammatory Panel 1; Human Eotaxin-2 Kit, a custom-designed 3-Plex kit, a custom-designed 1-Plex kit | CCL24 univariate analysis | IL-16, IL-7, VEGF-A, CXCL9, CX3CL1 univariate analysis; IL-16, IL-7, VEGF-A by multivariate cluster analysis | IL-17A, TNFβ, CCL19, CCL11, IL-1β, TNFα, CCL3, CCL17, CCL2, IFN-g, IL-15, CCL26, IL-6, IL-12/23p40, CCL22, IL-5, CCL13, IL-1α, CCL4, GM-CSF, IL-10, IL-4, IL-13, IL-2, CXCL10, IL-12p70, IL-8, B2M |
| Hardcastle et al. 2015 (126) | Fukuda et al. 1994 (71) | Serum | non-fasting blood sample | 8:30–11:30 a.m. | – | Multiplex | BioRad | BioPlex Pro human cytokine | IL-1β in moderate compared to severe ME/CFS; IL-7, IL-8, RANTES in moderate compared to severe ME/CFS and healthy controls; IFN-γ in severe compared to moderate ME/CFS | IL-6 in moderate compared to severe ME/CFS and healthy controls, | IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17, FGF, eotaxin, G-CSF, GM-CSF, IP-10, PDGF-BB, TNF-α and VEGF |
| Peterson et al. 2015 (127) | Fukuda et al. 1994 (71) | CSF | CSF samples via lumbar puncture | – | −80°C | Multiplex | BioRad | BioPlex Pro human cytokine | IL-10 | IL-1rα, IL-2, IL-6, IL-7, IL-8, IL-9, IL-12p70, IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, RANTES, TNF-α, and PDGF-BB | |
| Khaiboullina et al. 2015 (128) | Fukuda et al. 1994 (71) or ICC 2011 | Serum | x | – | −80°C | Multiplex | Bio-Rad Laboratories | Bio-Plex Human Cytokine 27-Plex Panel | CCL1, CCL2, CCL20, CCL3, CXCL10, IFNc, IL-1, IL-10, IL13, IL-1β, IL25, IL-31, IL-4, IL-6, IL-7, IL12 (p75), TNF | CCL11, CCL17, CCL19, CCL21, CCL25, CCL26, CCL3, CCL4, CCL5, CCL8, CSF1, CSF3, CX3CL1, CXCL1, CXCL13, CXCL6, CXCL8, HGF, IL-17F, IL5, IL-9, LIF, MIF, PDGF, TRAIL, VEGF | CCL13, CCL22, CCL23, CCL24, CCL27, CCL7, CXCL11, CXCL12a, CXCL12ab, CXCL13, CXCL16, CXCL2, CXCL5, CXCL9, FGF, GMCSF, IFN-α, IL-12 (p40), IL-15, IL-16, IL17A, IL-18, IL-1RA, IL-1α, IL-1b, IL-2, IL-21, IL-22, IL-23, IL-3, IL-33, IL-6, IL-2RA, LIF, sCD40L, SCF, SCGF-b, TNF-β, b-NGF |
| Wyller et al. 2015 (129) | Fukuda et al. 1994 (71) | Plasma | fasting bood samples | 7:30–9:30 a.m. | −80°C | Multiplex | Bio-Rad Laboratories | Bio-Plex Human Cytokine 27-Plex Panel | IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7. IL8, IL-9, IL-10, IL-12, IL-13, IL-17, IFN-c, CCL2, CCL3, CCL4, CCL5, CXCL10, PDGF-BB, VEGF, FGF, TNF | ||
| Hornig et al. 2015 (130) | Fukuda et al. 1994 (71) and Carruthers et al. 2003 (223) | Plasma | – | 10:00 a.m.−2:00 p.m. | −80°C | ELISA | Affymetrix | customized Procarta immunoassay | Leptin | Il-6, IL-8, IL-10, LT-a, IL17A, sFasL, CXCL10, MCSF, | TGF-β, IL-1β, IL-1α, TNF, IFN-α, IL-2, IL-12, IFN-c, IL-4, IL-13, IL-5, IL-15, IL-7, IL-13, IL-9, GMCSF, LIF, CD40L, TRAIL, CCL2, CCL3, CCL4, CCL5, CCL7, CCL11, CXCL1, CXCL5, CXCL9, PDGF-BB, VEGFA, sICAM-1, VCAM-1, TGF-α, FGFb, bNGF, HGF, SCF, GCSF |
| Neu et al. 2014 (131) | Fukuda et al. 1994 (71) | Serum | samples collected after 2nd night of polysomnography (indwelling cannula) | early morning | −20°C | Multiplex | BD Biosciences | CBA Human flex-set kit | IL-1β, TNF, IL8, IL-10 | IL-6, IFNc | |
| Nakatomi et al. 2014 (8) | Fukuda et al. 1994 (71) and ICC 2011 | Serum | – | – | −80°C | – | analyzed by the Mitsubishi Chemical Mediance Corps | – | IL-1β, IL-6, TNF, IFN-c | ||
| Garcia et al. 2014 (132) | Fukuda et al. 1994 (71) | Serum | x | – | – | Multiplex | Millipore | – | IL-6, IL-2, IL12, IFN-c, GMCSF, CXCL10 | IL-1β, IL-1α, IL-6, TNF, IL-8, IL-10, IFN-α, IL-4, LT-a, IL-5, IL-7, CCL2, CCL3, CCL4 | |
| Nakamura et al. 2013 (133) | Fukuda et al. 1994 (71) | Plasma | venous sampling throughout two nights, twice asleep and once awake (indwelling cannula) | 1:00, 3:00, 5:00, 8:00 a.m. | −80°C | Multiplex | Millipore | Milliplex human multicytokine detection system | IL-1β, IL-6, TNF, IL-8, IL-10, IL-4 | ||
| Maes et al. 2013 (134) | Fukuda et al. 1994 (71) | Plasma | fasting blood samples | 8:30–11:30 a.m. | – | ELISA | R&D, GE Healthcare UK Ltd. | Quantikine Human TNF-α Immunoassay; Amersham Interleukin-1 alpha ((h) IL-1α); Amersham Interleukin-1 beta ((h) IL-1β) | IL-1β, IL-1α, IFN-α | ||
| Lattie et al. 2012 (135) | Fukuda et al. 1994 (71) | Plasma | x | 11:00 a.m.−3:00 p.m. | −80°C | ELISA | Quansys Biosciences and R&D | Q-Plex Human Cytokine Screen; assayed in duplicate with R&D standard | IL-1β, IL-6 | TNF, IL-10, IL-2 | |
| Smylie et al. 2013 (136) | Fukuda et al. 1994 (71) | Plasma | blood drawn 3x during exercise challenge | – | −80°C | ELISA | Quansys Biosciences | Q-Plex Human Cytokine Screen (16-plex) | Males: IL-2, IL23 | Females: IL-1b, IL-1α, IL-6, TNF, IL-8, IL-10, IL-2, IL-12, IFN-c, IL-4, IL-13, TNF-β, IL-5, IL-23, IL-17, IL-15; Males: IL-1b, IL-1α, IL-6, TNF, IL-8, IL-10, IL-12, IFN-c, IL-4, IL-13, TNF-β, IL-5, IL-17, IL-15 | |
| Broderick et al. 2012 (137) | ICD (Reeves et al. 2005 (231) and Fukuda et al. 1994 (71)) | Plasma | fasting blood samples | Morning | −80°C | ELISA | Quansys Biosciences | Q-Plex Human Cytokine Screen (16-plex) | IL-8 | IL-23 | IL-1b, IL-1α, IL-6, TNF, IL-10, IFN-α, IL-2, IL-12, IFN-c, IL-4, IL-13, TNF-β, IL-5, IL-17, IL-15 |
| Maes et al. 2012 (138) | Fukuda et al. 1994 (71) | Plasma | fasting blood samples | 8:30–11:30 a.m. | – | ELISA | R&D, GE Healthcare UK Ltd. | Quantikine Human TNF-α Immunoassay; Amersham Interleukin-1 alpha ((h) IL-1α); Amersham Interleukin-1 beta ((h) IL-1β) | IL-1β, IL-1α, TNF | ||
| Nas et al. 2011 (139) | Fukuda et al. 1994 (71) | Serum | – | – | – | ELISA | DPC Immulite 1,000 Chemistry Analyzer | IMMULITE 10,00 analyzers, kits not specified | IL-6 | IL-8 | |
| White et al. 2010 (140) | Fukuda et al. 1994 (71) | Plasma | blood samples at baseline, 0.5, 8, 24, and 48 h post exercise | – | −80°C | Multiplex | Developed at the ARUP Institute for Clinical and Experimental Research (Salt Lake City, UT) | – | IL-1β, IL-6, TNF, IL-8, IL-10, IL-2, IL-12, IFN-c, IL-4, IL-13 | ||
| Nakamura et al. 2010 (141) | Fukuda et al. 1994 (71) | Plasma | venous sampling throughout the night while asleep (indwelling cannula) | 1:00, 3:00, 5:00, 8:00 a.m. | −80°C | Multiplex | Millipore | Beadlyte human multicytokine detection system 2 | IL-1β, IL-6, TNF, IL-8, IL-10, IL-4 | ||
| Nijs et al. 2010 (142) | Fukuda et al. 1994 (71) | Plasma | blood samples taken before and 1 h after exercise | – | – | ELISA | Amersham Biosciences Europe GmbH, Pierce Biotechnology Inc. | Biotrak Easy ELISA RPN5971, Endogen Human IL-1β ELISA kit | IL-1β | ||
| Robinson et al. 2010 (143) | Fukuda et al. 1994 (71) | Plasma | blood sampled at rest, at point of exhaustion, and 24 h post exercise (indwelling cannula); after overnight fast | – | – | ELISA | BD Biosciences | OptEIA | IL-6 | ||
| Scully et al. 2010 (144) | Fukuda et al. 1994 (71) | Plasma | x | – | −80°C | Multiplex | Meso Scale Discovery | – | IL-1β, IL-6, IL-8 | TNF, IL-10, IFN-c, IL-12p70, IL-13 | |
| Fletcher et al. 2009 (145) | Fukuda et al. 1994 (71) | Plasma | x | Morning | −80°C | Multiplex | Quansys Biosciences | Q-Plex Human Cytokine-Screen (16-plex) | IL-1β, IL-1α, IL-6, IL-12, IL4, IL-5 | IL-8, TNF-β, IL-15 | TNF, IL-10, IL-2, IFN-c, IL-13, IL-23, IL-17 |
| Jammes et al. 2009 (146) | Fukuda et al. 1994 (71) | Plasma | sampling throughout exercise protocol (indwelling cannula) | – | – | ELISA | R&D | Quantikine HS Human IL-6 Immunoassay D6050; Quantikine HS Human TNF-α DTA00C | IL-6, TNF | ||
| Nater et al. 2008 (147) | Fukuda et al. 1994 (71) | Plasma | fasting blood samples taken 30 minutes after indwelling cannula was placed | 7:30 a.m. | −80°C | ELISA | R&D | Quantikine HS Human IL-6 Immunoassay | Il-6 | ||
| Spence et al. 2008 (148) | Fukuda et al. 1994 (71) | Plasma and Serum | x | – | −70°C | ELISA | Mercodia, Kalon Biological, R&D | – | IL-1β, TNF | ||
| Vollmer-Conna et al. 2007 (149) | Fukuda et al. 1994 (71) | PBMC, Serum | blood samples taken 1, 2, 3, 6, and 12 months after infection onset | – | −80°C | Multiplex | Bioplex, BioRad | – | IL-1β, IL-2, IL-6, IL-10, IL-12, TNF, IFN-c | ||
| Kennedy et al. 2004 (150) | Fukuda et al. 1994 (71) | Platelet poor plasma | x | same time of day | – | ELISA | R&D | – | TGF-β | ||
| White et al. 2004 (151) | Fukuda et al. 1994 (71) | Plasma | blood collected 3 days after exercise | 9:30 a.m.−12:30 p.m. | – | ELISA | R&D | – | TGF-β | ||
| Visser et al. 2001 (152) | Fukuda et al. 1994 (71) | WBC | x | – | −20°C | ELISA | Pharmingen, R&D, Biorad | method from Cheney et al. 1989 (153) | TNFα, IL-10, IL-12, IFN-c | ||
| Cannon et al. 1999 (154) | Holmes et al. 1988 (80) | Plasma | collected 24 h post exercise | 9:00 a.m. | – | ELISA, radio-immunoassay (IL-1β) | R&D | – | IL-6 | ||
| Buchwald et al. 1997 (155) | Fukuda et al. 1994 (71) and Holmes et al. 1988 (80) | Serum | x | – | – | ELISA | Genzyme Diagnostics | Predicta | IL-6 | ||
| Bennett et al. 1997 (156) | Holmes et al. 1988 (80) | Serum | samples shipped on dry ice for 1 year before analysis | – | −20°C | Bioassay | R&D (IL-4-dependent HT-2 cell proliferation bioassay) | – | TGF-β | ||
| MacDonald et al. 1996 (157) | Holmes et al. 1988 (80) | Serum | x | 7:00–10:00 a.m. | – | ELISA | CCC (158) | For TGFβ: specially developed in a co-investigators lab; others not specified | TGF-β, IL-1β, IL-6, TNF | ||
| Swanink et al. 1996 (159) | Sharpe et al. 1991 (228) | WBC, Serum (TGFβ) | x | 8:30–11:00 a.m. | – | ELISA | R&D, Endogen | Measured as previously described in Drenth et al. 1995 (160); Quantikine (TGFβ) | TGF-β, IL-1β, IL-1α, TNF | ||
| Peterson et al. 1994 (161) | Holmes et al. 1988 (80) | Serum | blood collected at rest, immediately after exercise, and 40 min after exercise | – | −70°C | ELISA, bioassay (TGFβ) | R&D (ELISA and IL-4-dependent HT-2 cell proliferation bioassay) | Measured as previously described in Chao et al. 1991 (158) | TGF-β | IL-1β, IL-6, TNFα | |
| Patarca et al. 1994 (162) | Holmes et al. 1988 (80) | Plasma | once a month for 3 months | 7:30–10:30 a.m. | −20°C | ELISA | Endogen, R&D, Amersham, Genzyme | Intertest-4, Biokine | TNF | IL-1β, IL-1α, IL-6, IL-2, IL-4 | |
| Lloyd et al. 1994 (163) | RACP, 2002 (229) | Serum | blood was collected prior to, during, 15 min after, 4, 24 h post exercise (indwelling cannula) | – | −70°C | ELISA | Sucrosep; Centocor; Cistron Biotechnology; Biokine TNF | – | IL-1β, TNF, IFN-α, IFN-c | ||
| Linde et al. 1992 (164) | Holmes et al. 1988 (80) | Serum | serum collected < 7 days and 6 months after onset of mono | – | – | ELISA | T-Cell Sciences; IMMUNOtest Neopterin; Delfia; Medgenix; Quantikine R&D | – | IL-1α | IL-1β, IL-6, IFN-c | |
| Chao et al. 1991 (158) | Holmes et al. 1988 (80) | PBMC, Serum (TGFβ) | 1x a day, 5 consecutive days | 8:00–9:00 a.m. | −20°C | ELISA, bioassay (TGFβ) | R&D (ELISA and IL-4-dependent HT-2 cell proliferation bioassay) | – | TGF-β | IL-1β, IL-6, TNF, IL-2, IL-4 | |
| Straus et al. 1989 (165) | Holmes et al. 1988 (80) | Serum | x | – | −20°C | ELISA | Genzyme | sent to same laboratory as in Cheney et al. 1989 (153), no specifications | IL-1β, TNF, IFN-α, IL-2, IFN-c | ||
| Cheney et al. 1989 (153) | Holmes et al. 1988 (80) | Serum | biobank samples | – | – | ELISA | Genzyme | sent to Specialty Laboratories, LA, no specifications | IL-2 | ||
The articles compared in the table include the studies reviewed by Blundell et al. (104), as well as studies published since then (distinguished by the horizontal double line in the table). Stringer et al. (166) was not reviewed by Blundell et al. (104) but is included in the table. The newer studies were found by searching “myalgic encephalomyelitis,” “chronic fatigue syndrome,” or “myalgic encephalomyelitis/chronic fatigue syndrome” with “cytokine.” Studies were selected if they included an ME/CFS group and used a cytokine assay. Though not a systematic literature review, the studies in the table serve to show the variance in methodology (from sample collection and storage to assay selection) and reported results across cytokine studies. –, not specified/reported; x, no specifications of note for sample collection; CCC, Canadian Consensus Criteria; ICC, International Consensus Criteria; ICD, International Case Definition; RACP, Royal Australasian College of Physicians; SEID, Systemic Exertion Intolerance disease.
The corrected Table A1, Cytokine studies of ME/CFS appears below.
The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original table in the article has been updated.