Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue (CF) are distinct diagnostic categories with regard to clinical symptoms, severity of illness and biomarkers. Patients with ME and CFS show higher scores on fatigue, neurocognitive disorders, hyperalgesia, autonomic symptoms, postexertional malaise and a subjective feeling of infection than patients with CF. ME is characterized by increased postexertional malaise, a subjective feeling of infection and neurocognitive disorders and is a more severe variant than CFS.

Fukuda’s 1994 CDC criteria are adequate to make a distinction between patients with ME/CFS and CF, while ME/CFS patients should be subdivided into those with and without postexertional malaise into ME and CFS, respectively. Different interrelated pathophysiological mechanisms play a role in ME/CFS, i.e. (1) inflammation and immune activation, (2) oxidative and nitrosative stress and lowered antioxidant defenses, (3) activation of cell signaling networks, e.g. nuclear factor ĸβ, the 2 9 ,5 9 -oligoadenylate/RNase-L and/or protein kinase R pathway, (4) a transition towards autoimmune reactions, and (5) bacterial translocation.

The inflammatory biomarkers are higher in ME/CFS than in CF and higher in ME than in CFS. The above-mentioned pathways may explain the onset of characteristic ME/CFS symptoms, such as fatigue, malaise, autonomic symptoms, hyperalgesia, and neurocognitive symptoms. Different etiological factors may trigger ME/CFS/CF, e.g. viral and bacterial infections, and (auto)immune and inflammatory disorders, while psychosocial and physical stressors act as modulating factors. New pathophysiologically driven drug candidates for ME and CFS are discussed which target the pathways that play a role in ME/CFS.

Source: Maes M. Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome. Mod Trends Pharmacopsychiatri. 2013;28:162-74. doi: 10.1159/000343982. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/25224898