title: Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications.
abstract: BACKGROUND
  Evidence in support of intracellular immune dysfunctions in people with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is accumulating, but few studies have addressed intracellular immunity as a potential therapeutic target.
  
  
  OBJECTIVE
  To provide an overview of our present understanding of intracellular immunity in ME/CFS, to relate the intracellular immune dysfunctions to other aspects of the illness like decreased natural killer cell function, the presence of infections and poor exercise performance, and to point to potential therapeutic targets.
  
  
  METHODS
  An in-depth review of the scientific literature of intracellular immunity in people with ME/CFS was performed.
  
  
  CONCLUSIONS
  From the scientific literature it is concluded that proteolytic cleavage of the native RNase L enzyme is characteristic of the dysregulation of intracellular immunity in people with ME/CFS, but the origin of the dysregulation is speculative. There is increasing evidence for immune cell apoptosis and upregulation of various aspects of the 2'-5' oligoadenylate (2-5A) synthetase/RNase L pathway in ME/CFS. This review provides the theoretical rationale for conducting studies examining the effectiveness of direct or indirect drug targeting of the 2-5A synthetase/RNase L pathway in ME/CFS patients.
authors.affiliation: Vrije Universiteit Brussel, Faculty of Physical Education & Physiotherapy, Department of Human Physiology, Building L, Pleinlaan 2, 1050 Brussels, Belgium. Jo.Nijs@vub.ac.be <Jo.Nijs@vub.ac.be>
authors.forename: Jo
authors.initials: J
authors.lastname: Nijs
authors.forename: Marc
authors.initials: M
authors.lastname: Frémont
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007424:Intracellular Fluid / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*