Metabolic Brain Disease

, Volume 28, Issue 4, pp 523–540

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome

Authors

  • Gerwyn Morris
    • Tir Na Nog
    • Maes Clinics @ TRIA
    • Piyavate Hospital
Review Article

DOI: 10.1007/s11011-012-9324-8

Cite this article as:
Morris, G. & Maes, M. Metab Brain Dis (2013) 28: 523. doi:10.1007/s11011-012-9324-8

Abstract

This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this neuro-immune model.

Keywords

Chronic fatigue syndromeInflammationCytokinesDepressionTryptophanOxidative and nitrosative stressMitochondriaAutoimmune

Abbreviations

ME

Myalgic Encephalomyelitis

WHO

World Health Organization

CFS

Chronic fatigue syndrome

PICs

Pro-inflammatory cytokines

TNFα

Tumor necrosis factor

IL-6

Interleukin-6

NK

Natural killer

O&NS

Oxidative and nitrosative stress

NF-κB

Nuclear factor κB

2-5A

2′-5′-oligoadenylate

RNaseL

2-5A-dependent ribonuclease L

PKR

Protein kinase R

COX-2

Cyclo-oxygenase 2

IFNγ

Interferon γ

Th

T helper

TGF-β1

Transforming growth factor

Treg

T regulatory

ATP

Adenosine triphosphate

LPS

Lipopolysaccharide

TLR

Toll-like receptor

BBB

Blood brain barrier

SPECT

Single-photon emission computed tomography

PET

Positron emission tomography

T MRI

Tesla magnetic-resonance imaging

HPA

Hypothalamic-pituitary-adrenal

MS

Multiple sclerosis

IDO

2,3-dioxygenase

TRYCAT

Tryptophan catabolite

NMDA

N-methyl-D-aspartate

NADP

Nicotinamide adenine dinucleotide phosphate

STAT3

Signal Transducer and Activator of Transcription 3

Foxp3

Forkhead box P3

PBMCs

Peripheral blood mononuclear cells

SNPs

Single nucleotide polymorphisms

Copyright information

© Springer Science+Business Media, LLC 2012