Mitochondrial dysfunction and the role of cytokines in ME/CFS: Preliminary results from research being funded by The MEA Ramsay Research Fund and the Medical Research Council | 2 April 2015
From The FASEB Journal, published by the Federation of American Societies for Experimental Biology, April 2015.
The Role of Cytokines in Muscle Fatigue in Patients with Chronic Fatigue Syndrome (CFS)
Kate Earl(1), Giorgos Sakellariou(1), Daniel Owens(2), Melanie Sinclair(1), Manuel Fenech(1), Graeme Close(2), Clare Lawton(3), Louise Dye(3), Micheal Beadsworth(1) and Anne McArdle(1)
1) Institute of Ageing and Chronic Disease University of Liverpool United Kingdom
2) RISES Liverpool John Moores University United Kingdom
3) Psychological Sciences University of Leeds United Kingdom
CFS is characterized by profound levels of persistent/recurrent fatigue. It is proposed that chronic, low level inflammation may play a role in this fatigue.
We recruited 100 untreated patients with CFS (average age 33±12) and 100 age and sex matched healthy controls (HCs).
Serum levels of TNF-alpha were assessed using ELISA. Subjective fatigue was determined by questionnaire and muscle function tests were undertaken in subgroups in which maximal voluntary contraction (MVC), electrically stimulated muscle force generation and rate of fatigue were assessed in the quadriceps muscle.
Subjective fatigue was higher in patients with CFS compared with HCs. Preliminary analyses showed that serum TNF-alpha was undetectable in 97% of HCs, whereas 15% of patients with CFS had detectable (4.4+/-0.18pg/ml) serum TNF-alpha. MVC was significantly reduced in subjects with CFS compared with HCs.
No difference was seen in stimulated muscle fatigue between groups.
This preliminary data suggests that a sub-group of patients with CFS may have low level inflammation and analyses are underway to further characterise other inflammatory markers in serum and muscle of these patients and to determine whether such changes could affect indices of muscle function or central fatigue.
Funded by MRC, BBSRC and the ME Association.
COMMENT FROM DR CHARLES SHEPHERD, MEDICAL ADVISER, ME ASSOCIATION
Reprinted with the kind permission of the ME Association
These are important preliminary results from research into the role of mitochondrial dysfunction in ME/CFS that we are funding Professor Anne McArdle et al to carry out at the University of Liverpool.
Mitochondria are key cellular components that are responsible for the production of energy and the hypothesis underlying this research, which also involves the role of cytokines and low level inflammation, is as follows:
We hypothesise that the application of these newly developed techniques (at the University of Liverpool) will demonstrate that skeletal muscle mitochondria in patients with CFS are dysfunctional and that this results in muscle fatigue.
The dysfunctional mitochondria then activate a process which leads to a chronic, low grade inflammation, commonly reported in patients with CFS, which in turn results in further mitochondrial abnormalities and the establishment of a vicious circle of events.
Understanding the processes by which muscle fatigue occurs will lead to optimal interventions that break this vicious circle and improve muscle function and wellbeing of individuals.
These preliminary results from Liverpool add further support to research that has already been published, some of which has also been funded by the MEA Ramsay Research Fund, which indicates that there are abnormalities in skeletal muscle in at least a sub-group of people of that are not the result of deconditioning.
The preliminary results also support a role for cytokine induced inflammation in ME/CFS – as has been reported in the recently published research from Mady Hornig et al which has found important changes in certain specific cytokines in the early stages of ME/CFS in both blood and cerebrospinal fluid:
Among the other components to this muscle mitochondrial research we are funding is an examination of possible therapeutic interventions.
The MEA RRF is also helping to fund a study which is looking at mitochondrial DNA (= genetic material) in ME/CFS.
And we will be shortly announcing funding for a third mitochondrial function study.
Key research findings in ME/CFS relating to muscle and immunology are summarised and referenced in the Research section of the MEA purple booklet: ME/CFS/PVFS: An Exploration of the Key Clinical Issues