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Table 1 Overview of the different immune, inflammatory, oxidative and nitrosative stress (IO&NS) aberrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

From: Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways

Aberrations in the IO&NS pathways in ME/CFS Reference(s)
Increased production of key inflammatory mediators, such as NFκB, COX-2, iNOS Maes et al. [10], Maes et al. [11]
Increased levels of proinflammatory cytokines Fletcher et al. [12]
Immune activation, with increased in vivo expression of activation markers, such as CD38, and Th 1-like or Th 2-like responses Klimas et al. [13]
Immunosuppression, for example, diminished natural killer cell activity (NKCA), and decreased ex vivo expression of activation markers, such as CD69 Maher et al. [14], Mihaylova et al. [8]
Depleted antioxidant levels Maes et al. [15]
Increased levels of radical oxygen (ROS) and nitrogen species (RNS) Kennedy et al. [16]
Oxidative damage to membrane fatty acids, mitochondria, functional proteins and DNA Maes et al. [17], Behan et al. [18]
Autoimmune responses against oxidatively modified fatty acids and nitrated proteins (neoepitopes) Maes et al. [9]
Autoimmune reactions Maes (review) [19]
Gut dysbiosis and gut-derived inflammation with increased bacterial translocation Maes et al. [2022], Sheedy et al. [23]
Mitochondrial dysfunctions with lower carnitine and coenzyme Q10 levels Myhill et al. [24], Plioplys and Plioplys [25], Maes et al. [7]
Upregulation and dysregulation of the 2'-5' oligoadenylate synthetase/RNase L pathway Nijs and De Meirleir [26]
Apoptosis pathways Gow et al. [27], Kerr et al. [28]
Ion channel dysfunction (channelopathy) Broderick et al. [29]
Lowered omega-3 polyunsaturated fatty acids Maes et al. [30]
  1. For space considerations, this table only shows a selection of the relevant references. A more comprehensive listing can be supplied on request from the authors.
  2. COX-2: cyclo-oxygenase 2; iNOS = inducible nitric oxide synthase; NFκB = nuclear factor κB; Th = T helper.