Metab Brain Dis. 2012 Jun 21. [Epub ahead of print]
A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.
Morris G, Maes M.
Tir Na Nog, Pembrey, Llanelli, UK.
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.
This sort of research is brilliant. It’s good to know that very clever and knowledgeable people are working to help us – let’s wish them every success!
However, while there are ‘leads for future research’, what we really want to know is what to do about the problems outlined above; what’s the treatment?
This is the only mechanistic model that has been produced to explain ME. There should be no trouble working out real treatments from this, or biomarkers that will identify only those with this neuro-immune disease as opposed to the collection that has been swept up under the CFS banner.
It is a significant work and our Governments can no longer excuse keeping these neuro-immune patients in this diagnosis of exclusion (CFS). The CDC and NICE guidelines now need an urgent review and should be dispensed with for not being fit for purpose. Patients with a neuro-immune disease cannot think themselves better or exercise their system out of this pathology.