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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. [20–22], 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.