Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?
journal contributionposted on 2019-04-01, 00:00 authored by Gerwyn Morris, Michael Maes, Michael BerkMichael Berk, Basant K Puri
A model of the development and progression of chronic fatigue syndrome (myalgic encephalomyelitis), the aetiology of which is currently unknown, is put forward, starting with a consideration of the post-infection role of damage-associated molecular patterns and the development of chronic inflammatory, oxidative and nitrosative stress in genetically predisposed individuals. The consequences are detailed, including the role of increased intestinal permeability and the translocation of commensal antigens into the circulation, and the development of dysautonomia, neuroinflammation, and neurocognitive and neuroimaging abnormalities. Increasing levels of such stress and the switch to immune and metabolic downregulation are detailed next in relation to the advent of hypernitrosylation, impaired mitochondrial performance, immune suppression, cellular hibernation, endotoxin tolerance and sirtuin 1 activation. The role of chronic stress and the development of endotoxin tolerance via indoleamine 2,3-dioxygenase upregulation and the characteristics of neutrophils, monocytes, macrophages and T cells, including regulatory T cells, in endotoxin tolerance are detailed next. Finally, it is shown how the immune and metabolic abnormalities of chronic fatigue syndrome can be explained by endotoxin tolerance, thus completing the model.
JournalMetabolic brain disease
Pagination385 - 415
LocationNew York, N.Y.
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Publication classificationC1 Refereed article in a scholarly journal
Copyright notice2019, The Authors
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Chronic fatigue syndromeEndotoxin toleranceInflammationMitochondriaMyalgic encephalomyelitisOxidative and nitrosative stressScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismNeurosciencesNeurosciences & NeurologyHEART-RATE-VARIABILITYARYL-HYDROCARBON RECEPTORNITRIC-OXIDE SYNTHASENF-KAPPA-BCEREBRAL-BLOOD-FLOWSINGLE-NUCLEOTIDE POLYMORPHISMSSTATE FUNCTIONAL CONNECTIVITYPROTEIN S-NITROSYLATIONNECROSIS-FACTOR-ALPHATOLL-LIKE RECEPTORS