Format

Send to

Choose Destination
J Pharmacol Exp Ther. 2018 Oct;367(1):155-167. doi: 10.1124/jpet.118.250845. Epub 2018 Aug 3.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Author information

1
Second Department of Internal Medicine, Attikon General Hospital, Athens Medical School, Athens, Greece (E.H., M.A., G.D.); Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology (I.T., T.C.T.) and Sackler School of Graduate Biomedical Sciences (T.C.T.), Tufts University School of Medicine, Boston, Massachusetts; and Departments of Internal Medicine and Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts (T.C.T.).
2
Second Department of Internal Medicine, Attikon General Hospital, Athens Medical School, Athens, Greece (E.H., M.A., G.D.); Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology (I.T., T.C.T.) and Sackler School of Graduate Biomedical Sciences (T.C.T.), Tufts University School of Medicine, Boston, Massachusetts; and Departments of Internal Medicine and Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts (T.C.T.) theoharis.theoharides@tufts.edu.

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with associated malaise, headaches, sleep disturbance, and cognitive impairment, which severely impacts quality of life. A significant percentage of ME/CFS patients remain undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers. ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown, preventing the development of effective treatments. The ME/CFS phenotype has been associated with abnormalities in energy metabolism, which are apparently due to mitochondrial dysfunction in the absence of mitochondrial diseases, resulting in reduced oxidative metabolism. Such mitochondria may be further contributing to the ME/CFS symptomatology by extracellular secretion of mitochondrial DNA, which could act as an innate pathogen and create an autoinflammatory state in the hypothalamus. We propose that stimulation of hypothalamic mast cells by environmental, neuroimmune, pathogenic and stress triggers activates microglia, leading to focal inflammation in the brain and disturbed homeostasis. This process could be targeted for the development of novel effective treatments.

PMID:
30076265
DOI:
10.1124/jpet.118.250845

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center