A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID)

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Abstract

Background

Cytokines in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) patients compared with healthy controls have been extensively studied. However, the evidence regarding whether a baseline difference between CFS/ME/SEID patients and the normal population remains unclear. The aim of this study was to conduct a systematic review of the literature regarding cytokines in CFS/ME/SEID and whether there is a significant difference in cytokine levels between this patient group and the normal population.

Methods

Pubmed, Scopus, Medline (EBSCOHost), and EMBASE databases were searched to source relevant studies for CFS/ME/SEID. The review included any studies examining cytokines in CFS/ME/SEID patients compared with healthy controls. Results of the literature search were summarised according to aspects of their study design and outcome measures, namely, cytokines. Quality assessment was also completed to summarise the level of evidence available.

Results

A total of 16,702 publications were returned using our search terms. After screening of papers according to our inclusion and exclusion criteria, 15 studies were included in the review. All the included studies were observational case control studies. Ten of the studies identified measured serum cytokines in CFS/ME/SEID patients, and four measured cytokines in other physiological fluids of CFS/ME/SEID patients. The overall quality assessment revealed most papers included in this systematic review to be consistent.

Conclusions

Despite the availability of moderate quality studies, the findings of this review are inconclusive as to whether cytokines play any definitive role in CFS/ME/SEID, and consequently, they would not serve as reliable biomarkers. Therefore, in light of these results, it is recommended that further efforts toward a diagnostic test and treatment for CFS/ME/SEID continue to be developed in a range of research fields.

Electronic supplementary material

The online version of this article (10.1186/s12883-019-1433-0) contains supplementary material, which is available to authorized users.

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Most cited references 24

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Multiplex bead array assays: performance evaluation and comparison of sensitivity to ELISA.

J. Philip McCoy, Mohamed Elshal (2006)

The measurement of soluble cytokines and other analytes in serum and plasma is becoming increasingly important in the study and management of many diseases. As a result, there is a growing demand for rapid, precise, and cost-effective measurement of such analytes in both clinical and research laboratories. Multiplex bead array assays provide quantitative measurement of large numbers of analytes using an automated 96-well plate format. Enzyme-linked immunosorbent assay (ELISAs) have long been the standard for quantitative analysis of cytokines and other biomarkers, but are not well suited for high throughput multiplex analyses. However, prior to replacement of ELISA assays with multiplex bead array assays, there is a need to know how comparable these two methods are for quantitative analyses. A number of published studies have compared these two methods and it is apparent that certain elements of these assays, such as the clones of monoclonal antibodies used for detection and reporting, are pivotal in obtaining similar results from both assays. By careful consideration of these variables, it should be possible to utilize multiplex bead array assays in lieu of ELISAs for studies requiring high throughput analysis of numerous analytes.

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A community-based study of chronic fatigue syndrome.

Christine K. Jordan, Carin M. A. Rademaker, W A McCready … (1999)

Most previous estimates of the prevalence of chronic fatigue syndrome (CFS) have derived largely from treated populations, and have been biased by differential access to health care treatment linked with sex, ethnic identification, and socioeconomic status. To assess the point prevalence of CFS in an ethnically diverse random community sample. A sample of 28,673 adults in Chicago, Ill, was screened by telephone, and those with CFS-like symptoms were medically evaluated. MAIN OUTCOME MEASURES AND ANALYSES: Self-report questionnaires, psychiatric evaluations, and complete medical examinations with laboratory testing were used to diagnose patients with CFS. Univariate and multivariate statistical techniques were used to delineate the overall rate of CFS in this population, and its relative prevalence was subcategorized by sex, ethnic identification, age, and socioeconomic status. There was a 65.1% completion rate for the telephone interviews during the first phase of the study. Findings indicated that CFS occurs in about 0.42% (95% confidence interval, 0.29%-0.56%) of this random community-based sample. The highest levels of CFS were consistently found among women, minority groups, and persons with lower levels of education and occupational status. Chronic fatigue syndrome is a common chronic health condition, especially for women, occurring across ethnic groups. Earlier findings suggesting that CFS is a syndrome primarily affecting white, middle-class patients were not supported by our findings.

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Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Ekua W Brenu, Mieke van Driel, Don Staines … (2011)

Background Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers) in CFS/ME patients. Methods We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK) and CD8+T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4+T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2), levels of NK phenotypes (CD56bright and CD56dim) and regulatory T cells expressing FoxP3 transcription factor. Results Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NK phenotypes, in particular the CD56bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients. Conclusions Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

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Author and article information

Contributors

Matthew Corbitt:

ORCID: http://orcid.org/0000-0002-3156-6731

+56789283 , ncned@griffith.edu.au

Natalie Eaton-Fitch: natalie.eaton-fitch@griffithuni.edu.au

Donald Staines: d.staines@griffith.edu.au

Hélène Cabanas: h.cabanas@griffith.edu.au

Sonya Marshall-Gradisnik: s.marshall-gradisnik@griffith.edu.au

Journal

Journal ID (nlm-ta): BMC Neurol

Journal ID (iso-abbrev): BMC Neurol

Title: BMC Neurology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2377

Publication date (Electronic): 24 August 2019

Publication date PMC-release: 24 August 2019

Publication date Collection: 2019

Volume: 19

Electronic Location Identifier: 207

Affiliations

[1 ]ISNI 0000 0004 0437 5432, GRID grid.1022.1, National Centre for Neuroimmunology and Emerging Diseases, , Menzies Health Institute, Griffith University, ; Gold Coast, Australia

[2 ]ISNI 0000 0004 0437 5432, GRID grid.1022.1, School of Medical Science, Griffith University, ; Gold Coast, Australia

[3 ]ISNI 0000 0004 0437 5432, GRID grid.1022.1, Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, , Griffith University, ; Gold Coast, QLD Australia

Author information

Matthew Corbitt http://orcid.org/0000-0002-3156-6731

Article

Publisher ID: 1433

DOI: 10.1186/s12883-019-1433-0

PMC ID: 6708220

PubMed ID: 31445522

SO-VID: d0a0ffdb-ab69-41d8-93cc-9c1f866ccb09

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 27 August 2018

Date accepted : 18 August 2019

Funding

Funded by: Stafford Fox Medical Research Foundation

Funded by: Mason Foundation

Funded by: Mr Douglas Stutt

Funded by: Blake Beckett Foundation

Funded by: McCusker Charitable Foundation

Funded by: Alison Hunter Memorial Foundation

Funded by: Change for ME Charity

Funded by: Ian and Talei Stewart and the Change for ME Charity

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ScienceOpen disciplines: Neurology

Keywords: chronic fatigue syndrome,myalgic encephalomyelitis,systemic exertion intolerance disease,cytokines

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ScienceOpen disciplines: Neurology

Keywords: chronic fatigue syndrome, myalgic encephalomyelitis, systemic exertion intolerance disease, cytokines

A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID)

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Most cited references 24

Multiplex bead array assays: performance evaluation and comparison of sensitivity to ELISA.

A community-based study of chronic fatigue syndrome.

Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

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