For for the past 20 years I have conducted research on how and why increased activity of the immune and inflammatory systems is involved in the regulation of mood and fatigue. We all know how awful we feel when we experience increased inflammation in the body, because of high fever during an infection or a bout of an inflammatory disorder such as rheumatoid arthritis: we feel physically and mentally tired.
While these milder symptoms are miles away from the debilitating, enduring mental and physical fatigue that characterise ME/CFS, I believe that shared mechanisms related to the immune system could be dysfunctional in all these different conditions, albeit with much stronger and abnormal changes in the ME/CFS group.
The notion that the immune and inflammatory systems is involved in ME/CFS is not new, but now we have the technical and laboratory procedures to truly dissect these mechanisms. For example, for many years we have known that a notable proportion of patients with ME/CFS report symptoms of infections at the outset of the disorder, or at times of re-exacerbations.
Moreover, our own work (funded by the Medical Research Council through its Understanding the mechanisms of CFS/ME initiative) has demonstrated that individuals who experience prolonged activation of the immune system, as part of the treatment for viral infection, experience intense fatigue not only when the immune system is activated but also many months after, when the immune system returns to normal. This suggests that an activation of the immune system, and the resulting inflammation in the body, can leave a ‘physical scar’ that persists weeks or months after this activation is resolved – and that this scar may be part of the process leading to ME/CFS, at least in some patients.
But, as often happens for medical conditions, mechanisms underlying illnesses are shared and overlapping between different disorders, and we now know that increased activity of the immune system is present in a range of pathologies, from diabetes and metabolic disorders to depression and mood disorders. Hence the need that research on ME/CFS – and especially research on the immune system and ME/CFS – must choose appropriate comparison groups as well as exclude individuals in which fatigue may be the consequence of another mental or physical disorder, and not true cases of ME/CFS.
The launch of MEGA, with the opportunity to explore a variety of biological mechanisms (including immune and inflammatory mechanisms) in the largest ever group of people with ME/CFS (and adequate comparison groups), will increase exponentially our ability to understand how and why increased activity of the immune and inflammatory system is involved in this disabling condition. I am looking forward to working with my colleagues and the patient community to maximise the benefits that this initiative will bring.