Title:Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)
Volume: 12
Issue: 2
Author(s): Gerwyn Morris and Michael Maes
Affiliation:
Keywords:
Autoimmune, chronic fatigue syndrome, cytokines, inflammation, myalgic encephalomyelitis, nitrosative stress,
oxidative.
Abstract: Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the
central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost
bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a
chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS
and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological
processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immuneinflammatory
pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation,
autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased
antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are
brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and
peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against
disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism
(e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these
factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and
autoimmune pathways which may sustain the disease.
