title: Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response.
abstract: The exacerbation of symptoms after exercise differentiates Chronic fatigue syndrome (CFS) from several other fatigue-associated disorders. Research data point to an abnormal response to exercise in patients with CFS compared to healthy sedentary controls, and to an increasing amount of evidence pointing to severe intracellular immune deregulations in CFS patients. This manuscript explores the hypothetical interactions between these two separately reported observations. First, it is explained that the deregulation of the 2-5A synthetase/RNase L pathway may be related to a channelopathy, capable of initiating both intracellular hypomagnesaemia in skeletal muscles and transient hypoglycemia. This might explain muscle weakness and the reduction of maximal oxygen uptake, as typically seen in CFS patients. Second, the activation of the protein kinase R enzyme, a characteristic feature in atleast subsets of CFS patients, might account for the observed excessive nitric oxide (NO) production in patients with CFS. Elevated NO is known to induce vasidilation, which may limit CFS patients to increase blood flow during exercise, and may even cause and enhanced postexercise hypotension. Finally, it is explored how several types of infections, frequently identified in CFS patients, fit into these hypothetical pathophysiological interactions.
authors.affiliation: Department of Human Physiology, Faculty of Physical Education and Physical Therapy Science, Vrije Universiteit Brussel, Brussel 1090, Belgium. jo.nijs@vub.ac.be
authors.forename: Jo
authors.initials: J
authors.lastname: Nijs
authors.forename: Kenny
authors.initials: K
authors.lastname: De Meirleir
authors.forename: Mira
authors.initials: M
authors.lastname: Meeus
authors.forename: Neil R
authors.initials: NR
authors.lastname: McGregor
authors.forename: Patrick
authors.initials: P
authors.lastname: Englebienne
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D015444:Exercise; D015673:Fatigue Syndrome, Chronic / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D018448:Models, Immunological; D009119:Muscle Contraction; D018763:Muscle Fatigue / Q000276:immunology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase