The DOI matches its Crossref record; 207 of the 207 references it cites were found in a registry or an index.
A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome
Abstract
This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this neuro-immune model.
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“Thus, HPG dysregulation may increase blood-brain barrier permeability, allowing infiltration of immune cells into the brain to establish or sustain a low-grade neuroinflammatory profile as put forward by Morris and Maes17.”
From Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically-relevant Phenotyping of Women with Chronic Fatigue Syndrome (2019) · cites this paper as [17]
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Cites
Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178
Free Radicals in Biology and Medicine
Halliwell, B., & Gutteridge, J. M. C. (2015) · doi:10.1093/acprof:oso/9780198717478.001.0001 · Cited by 8,990
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study
Fukuda, K., Straus, S. E., Hickie, I., Sharpe, M. C., Dobbins, J. G., Komaroff, A., & and International Chronic Fatigue Syndrome Study Group. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-121-12-199412150-00009 · Cited by 4,969 · cited 6×
“According to a commonly used diagnostic classification of CFS (Fukuda et al. 1994), chronic fatigue must be accompanied by four or more of the following symptoms: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multi-joint pain without…”
BackgroundMethodInfluentialKorn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728
Paxinos, G. (1985) · Cited by 3,715
Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452
Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration
Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R., Hong, J., Knapp, D. J., & Crews, F. T. (2007) · Glia · doi:10.1002/glia.20467 · Cited by 2,144
Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases
Simopoulos, A. P. (2002) · Journal of the American College of Nutrition · doi:10.1080/07315724.2002.10719248 · Cited by 2,060
Research works printed but not linked: 1
- Pincus S (2005) Potential role of infections in chronic inflammatory diseases. ASM News 71:529–535
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Lucas, K., & Maes, M. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8425-7 · Cited by 466
Self-citationThe many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders
Morris, G., & Berk, M. (2015) · BMC Medicine · doi:10.1186/s12916-015-0310-y · Cited by 245
Self-citationShukla, S. K., Cook, D., Meyer, J., Vernon, S. D., Le, T., Clevidence, D., Robertson, C. E., Schrodi, S. J., Yale, S., & Frank, D. N. (2015) · PLOS ONE · doi:10.1371/journal.pone.0145453 · Cited by 137
Smith, M. E. B., Haney, E., McDonagh, M., Pappas, M., Daeges, M., Wasson, N., Fu, R., & Nelson, H. D. (2015) · Annals of Internal Medicine · doi:10.7326/m15-0114 · Cited by 142
“Some propose that an inciting event initiates an immune response that leads to immune and neuroendocrine dysregulation (10, 11).”
BackgroundMorris, G., Anderson, G., Berk, M., & Maes, M. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8477-8 · Cited by 96
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Metadata
- Authors
- Morris, G., & Maes, M.
- Affiliations
- Piyavate Hospital (TH)
- Corresponding author
- Maes, Michael
- Venue
- Metabolic Brain Disease
- Published
- 2012-06-21
- Volume
- 28
- Issue
- 4
- Pages
- 523-540
- ISSN
- 0885-7490 (ISSN-L)
- 1573-7365
- OpenAlex
- W2035315327
- Cited by
- 117
- References
- 207
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 1 · 2019: 11 · 2018: 7 · 2017: 5 · 2016: 14 · 2015: 16 · 2014: 9 · 2013: 14
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Metabolic Brain Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- World Health Organization
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- chronic fatigue syndrome, inflammatory cytokines, NF-κB, mitochondrial dysfunction, autoreactive T cells, autoimmunity, molecular mimicry, bystander activation, epitope spreading, microglial activation, vagus nerve, post-exertional malaise, immune activation
- MeSH terms
- Brain, Fatigue, Humans, Inflammation, Models, Biological, Fatigue Syndrome, Chronic, Cytokines, Oxidative Stress
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