title: Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms.
abstract: OBJECTIVE
  The aim of this paper is to review recent findings on inflammatory and oxidative and nitrosative stress (IO&NS) pathways in chronic fatigue and somatization disorder.
  
  
  RESULTS
  Activation of IO&NS pathways is the key phenomenon underpinning chronic fatigue syndrome (CFS): intracellular inflammation, with an increased production of nuclear factor kappa beta (NFkappabeta), cyclo-oxygenase-2 (COX-2) and inducible NO synthase (iNOS); and damage caused by O&NS to membrane fatty acids and functional proteins. These IO&NS pathways are induced by a number of trigger factors, for example psychological stress, strenuous exercise, viral infections and an increased translocation of LPS from gram-bacteria (leaky gut). The 'psychosomatic' symptoms experienced by CFS patients are caused by intracellular inflammation (aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection); damage caused by O&NS (aches and pain, muscular tension and fatigue); and gut-derived inflammation (complaints of irritable bowel). Inflammatory pathways (monocytic activation) are also detected in somatizing disorder.
  
  
  CONCLUSIONS
  'Functional' symptoms, as occurring in CFS and somatization, have a genuine organic cause, that is activation of peripheral and central IO&NS pathways and gut-derived inflammation. The development of new drugs, aimed at treating those disorders, should target these IO&NS pathways.
authors.affiliation: Clinical Research Centre of Mental Health (CRC-MH), Antwerp, Belgium. crc.mh@telenet.be
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D016207:Cytokines / Q000378:metabolism; D015673:Fatigue Syndrome, Chronic / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation; D053858:Metabolic Networks and Pathways; D015538:Nitrosation; D018384:Oxidative Stress; D011602:Psychophysiologic Disorders / Q000503:physiopathology*; D013001:Somatoform Disorders / Q000503:physiopathology*; D013312:Stress, Physiological
chemical_list: D016207:Cytokines