King’s College: Clues to chronic fatigue syndrome in overactive immune response | 17 December 2018

December 17, 2018


The words below come from the King's College IOPPN website unless otherwise indicated.

“Our findings suggest that people who have an exaggerated immune response to a trigger may be more at risk of developing CFS.”

New research from King’s College London finds that an exaggerated immune response can trigger long-lasting fatigue, potentially explaining how chronic fatigue syndrome (CFS) begins. The study is the most in-depth biological investigation yet into the role of the immune system in lasting symptoms of fatigue.

CFS, also known as myalgic encephalomyelitis (ME), is a long-term illness which is characterised by extreme tiredness. The underlying biology of CFS has remained a mystery, hampering the search for treatments. There is some evidence that the immune system plays a role in triggering CFS and many patients report their illness starting with a challenge to the immune system such as a viral illness.

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By the time patients are diagnosed it is too late to catch CFS in its earliest stages, and it is impossible to assess the biology of patients before the illness develops. To get around this problem, researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) used a model for CFS based on a treatment for hepatitis C called interferon-alpha.

Interferon-alpha activates the immune system in the same way as a powerful infection. A lot of patients develop acute fatigue during treatment with interferon-alpha and a minority go on to have a CFS-like illness, where fatigue lasts for more than six months after the treatment ends.

The researchers measured fatigue and immune system markers in 55 patients before, during and after treatment with interferon-alpha, tracking which people developed the persistent CFS-like illness.

The team found differences in the immune systems of 18 patients who developed lasting fatigue compared to those who recovered as normal.

During treatment with interferon-alpha there was a much bigger immune response among those who developed the CFS-like illness, with a doubling in the levels of immune system ‘messenger’ molecules interleukin-10 and interleukin-6.

Importantly, even before treatment started, levels of interleukin-10 were higher among those who went on to have lasting fatigue, suggesting the immune system may have been ‘primed’ to over-respond.

Lead researcher Dr Alice Russell from the IoPPN says: ‘For the first time, we have shown that people who are prone to develop a CFS-like illness have an overactive immune system, both before and during a challenge to the immune system. Our findings suggest that people who have an exaggerated immune response to a trigger may be more at risk of developing CFS.’

“Piecing together the scientific jigsaw, it now seems increasingly likely that we are dealing with a sequence of events in ME/CFS that involve both infection and the immune system response.”


“A straightforward viral infection is leading to a immune system reaction that then fails to settle down.”


“And the on-going production of inflammation then causes immune system chemicals that affect various parts of the body – muscle and brain function in particular.”


“These findings also reinforce the need to investigate treatments – as are being used very successfully in inflammatory conditions like rheumatoid arthritis – which can dampen down low-level immune system activation.”


Dr Charles Shepherd, Hon. Medical Adviser, ME Association quoted today in The Telegraph, and also by BBC Health.

By the time the CFS-like illness developed, however, there was no longer any detectable difference in the immune system of patients compared to those who recovered as normal. As well as looking at people having interferon-alpha treatment, the researchers also found no difference in immune activation between 54 people with diagnosed CFS and 57 healthy controls.

Alongside the overactive immune response, those people who developed the CFS-like illness had more acute fatigue during treatment with interferon-alpha than people who recovered as normal. Yet before treatment there was no difference between the groups in their levels of fatigue or in any psychiatric symptoms like depression or recent stressful life-events.

Senior researcher Professor Carmine Pariante from the IoPPN says: ‘A better understanding of the biology underlying the development of CFS is needed to help patients suffering with this debilitating condition.’

‘Although screening tests are a long way off, our results are the first step in identifying those at risk and catching the illness in its crucial early stages. Confirmation is needed that the findings from people treated with interferon-alpha apply to people with CFS, and future work to better understand the factors that may be driving an exaggerated immune response is required.’

Dr Neha Issar-Brown, Head of Population and Systems Medicine at the Medical Research Council, which funded the research, said: ‘CFS/ME is a serious condition and its underpinning biology is poorly understood. Encouragingly, this work sheds light on potential mechanisms of immune dysregulation underlying early stages of chronic fatigue syndrome. The MRC strongly encourages more research to better understand this condition in order to address an area of unmet clinical need.’

Paper reference

Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of Chronic Fatigue Syndrome Russell et alPsychoneuroendocrinology, DOI:


4 thoughts on “King’s College: Clues to chronic fatigue syndrome in overactive immune response | 17 December 2018”

  1. A welcome early Christmas present for sufferers and their carers. This ‘mystery’illness has blighted my life for 20 years, during which time sufferers have heard of many ‘breakthroughs ‘ and ‘miracle ‘ cures,so we are not about to start doing cartwheels (chance would be a fine thing) but these results sound promising. At least it is yet another nail in the coffin of the,” it’s all in the mind” brigade,and may quieten their psychosocial babble,however I won’t be holding my breath. I hope these findings are made compulsory reading for all GPs and that as a consequence they desist from dishing out tranquillisers and begin to view CFS/ME as a biological illness.At the very least these results,and the comprehensive media coverage they have provoked, should help explain the condition to a hitherto sceptical and often dismissive public- not to mention friends and family. We ‘live’ in hope,where would we be with out it. Happy Christmas to all my fellow sufferers and their carers,and let’s hope 2019 brings more biological research with even more positive findings. I look forward in hope rather than expectation to NICE speeding up their review,or perhaps an interim amendment to their guidelines ending the reign of CBT and GET! Ciaran

  2. This research is most welcome, but it is a pity that on Radio 4 Dr Carmine Pariante was equivocal on the distinction between mental and physical illness. He argued that they are synonymous. It’s all just “health”. Yet according to his own research, “before treatment there was no difference between the groups in their levels of fatigue or in any psychiatric symptoms like depression or recent stressful life-events.” Therefore the development of ME/CFS like symptoms following treatment is unlikely to be psychosomatic. Similarly, as Professor Lubet points out, “No reputable physician would claim that cancer is reversible through exercise and psychotherapy, much less boast about subsequent recovery rates.” Yet cancer can sometimes be cured by biological treatments. The only rational inference from this observation is that mental and physical illness are not synonymous but distinct.

  3. I was in bed when I heard Dr Pariante, so wasn’t fully with it, but I took him to mean that there are psychological symotoms to most illnesses, in as much as illness have an effect on mental health, such as mood, depression, etc.

    I was particularly interested in this research, although I have heard the theory before, as I believe this yrs’ flu jab is to blame for my current relapse. I have had them annual,y for many years, with no serious consequences, but this year it seems to have hit me esp. hard. As this yrs’ has included an immune booster I wondered whether that could be the cause, as an immune booster with an already compromised immune system could have a negative effect.

    I wondered whether anyone had had similar problems this year, or know of others who had. Or is it just me?

  4. Hi Caroline,I trust you had an enjoyable Christmas despite your relapse. I was interested to read your comments concerning this years flu jab,like you I have had the jab for many years,seemingly without any adverse effects,but this year I have also suffered a relapse.I had not connected the two until I read your hypothesis and it would certainly explain my current setback if you were correct. I will be looking very closely at the situation next winter before I decide whether or not to continue having the jab. May I ask how you discovered that this years contained an “immune booster”? Ciaran

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