Persistent fatigue induced by interferon-alpha: A novel, inflammation-based, proxy model of Chronic Fatigue Syndrome, 2018, Pariante et al

The radio 4 continues the mystery notion. This isn’t a complete mystery with this one chink of light now from our MRC and psychiatry saviours. The patient is actually quite good thankfully, although a short Time case usually preferred by the media . I don’t really accept CP as an ME expert, , I can see why he’s a SMC favoured CFS spokesman form what he said, PEM vs fatigue wasn’t conveyed at all.
 
In 1987 a fellow member of our ME support group had been treated with interferon. I think he was part of a study but it was long ago. It had not helped him.

We are not being too nitpicking. This study says nothing at all about ME as the cardinal symptom of PEM was not looked for. It may say something about fatigue, but I did not experience fatigue for decades after I developed ME (i still have very little actual fatigue).

I have fatiguability with no warning. Some days I could walk miles, other days I could go a few steps. I never knew what would happen and the stop was sudden and complete.

Now something was broken inside me when I took the originating virus. It may be because of immune problems I do not know and this study does nothing to answer it. While it may be useful to counteract that we have a psychological problem talking and actually listening to patients for a few minutes could tell them that.

This study and press hype is another example of the same group of researchers making up an illness and saying it is what we have. because they invented it they can claim whatever they like about the causes and perpetuating factors. It is designed to benefit the researchers not to help patients.
 
Jonathan Edwards said:
I am not sure interferon alpha was available in 1988 but it may have been some time around then.
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Possibly 25 years. :) I have a memory of lying in bed reading the AfME newsletter and reading about this mysterious but proper-sounding stuff, interferon-alpha. Although that sounds too precise to be a genuine memory and one that my brain hasn't helpfully just this minute supplied...
 
Jonathan Edwards said:
I think people are being too nitpicking. I agree with Simon. The basic study here is useful in documenting the fact that a known immunological stimulus can cause a long term and severe illness characterised by fatigue. That may not be the same as CFS or ME but it shows that you do not need to postulate any psychological factors in the causation of an illness at least similar to ME in some respects. A small step but an important one.

I detect a certain reluctance by people to take this seriously - just a bit of fatigue or whatnot. I can assure everyone that interferon alpha induced fatigue can be every bit as debilitating as PWME describe. I had one patient who was devastated by interferon. Moreover, it did not work for him and he died of his Hepatitis after a couple of years of being unable to do anything for himself.

This is not a useful model for MS because we already know that MS is due to an immunological abnormality that we can identify pathologically and with imaging. There is no need to model MS to show that you can be paralysed permanently by an immune stimulus. We know that. And if interferon alpha induced illness makes it more plausible to put ME on a par with MS surely that is useful?

I have not looked at the recent abstract to see what data it contains. I suspect it shows some slight shifts in cytokines that do not take us much further. But the original observation that illness persists after interferon alpha in some people without any obvious inflammatory response long term is to me important. You do not need large numbers for this sort of finding. We know that it is a not insignificant minority and not just a rare quirk. I think maybe the biggest criticism one can make of the recent work is that it has not really told us anything more than we knew before the study started. But getting detailed documentation of phenomena like this from prospective studies is always worthwhile because sometimes it turns something important up.
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To put it another way: this is useful because it shows that illness can persist despite the absence of obvious markers. It's a major nail in the coffin of the 'no abnormalities = no problem' narrative.

The study also expressly says (I know I'm repeating myself, but this is important):
This lower KYN/TRP ratio in CFS (and the lack of association with PF) is somewhat in opposition to a study of somatization which observed higher levels of the KYN/TRP ratio (Maes et al., 2011). This evidence points again to a different biological underpinning of primarily psychiatric syndromes, such as depression and somatization, as opposed to CFS. This notion is further supported by the lack of an association, in our study, between PF and any of the classic, stress-related risk factors for psychiatric disorders. Targeting the kynurenine pathway, through antidepressants or nutritional interventions, may thus not be a relevant therapeutic strategy in CFS (Borsini et al., 2017).
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Jonathan Edwards said:
I am not sure interferon alpha was available in 1988 but it may have been some time around then.
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Smith et al (1988)(Smith, Tyrell, Coyle and Higgins. Effects of interferon alpha on performance in man; a preliminary report . Psychopharmacology 96 414-416) injected normal volunteers with alpha interferon and those receiving 1.5Mu of interferon developed symptoms which closely resembled influenza. They also showed identical changes in performance to those shown by people with influenza, with some function being impaired but others remaining intact. Furthermore, after effects of interferon challenge were observed even though the symptoms had disappeared .

Cognitive Changes in Myalgic encephalomyelitis. Andrew Smith in Post viral fatigue syndrome (ME) 1991 eds Jenkins and Mowbray.

Edited to include date and italics
 
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I think I would have found this an interesting study if they presented it as a study of persisting fatigue that can be relevant for conditions like ME/CFS.

As Simon pointed out, persisting fatigue was not associated with psychosocial factors (history of depression, stressful life event, early life trauma etc.) but with immune factors like IL-6 and IL-10. The interesting thing is that the between group differences in cytokines were only visible in the beginning of the IFN-α treatment, even though the fatigue persisted for months afterwards. So if these patients were to go to a fatigue clinic, doctors would not be able to find differences in these immune markers. This study however showed that there were differences at the early stage, a time point that doctors normally can’t see.

The results very much contradict everything Wessely and Sharpe have been saying about patients with chronic fatigue. I guess psychosocial factors were only measured at baseline, but there would have to be some pretty dramatic psychological change for their cognitive behavioral model to be of any relevance to these patients. I think White Buchwald, Jason and the Dubbo studies previously found similar results (psychosocial factors are irrelevant) in patients with postinfectious CFS, so their model seems to have been proven wrong by the data.


I agree that it’s dubious to see persisting fatigue in this study as a proxy for ME/CFS. For one, on the Chalder fatigue scale, they showed much less fatigue (17) than patients selected by the oxford criteria (26).


There was an interesting finding regarding the kynurenine to tryptophan (KYN/TRP) ratio, which was lower in the (Oxford criteria) 54 CFS patients compared to controls. A Maes study previously found KYN/ TRP ratio to be higher in patients with depression and somatization. The oxford criteria can be misleading but maybe it’s a good idea as Anton Mayer did, to get Periante interested into researching this into more depth, with reference to Phairs metabolic trap hypothesis?

 
Pariante on radio on mental versus physical wasn’t helpful. Whilst psychiatric illness might have biological underpinnings it presents primarily as issues with mood and behaviour, physical illnesses primarily present with physical symptoms. Whilst dementia might sit in both courts arthritis is a physical illness not a mental one, so is MS , why is it with ME that suddenly all boundaries and classification is unacceptable when most pwME do not have major MH presentation.
 
Blog from the ME Association, can't say I'm particularly impressed with the part that I've bolded below.
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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https://www.meassociation.org.uk/20...-overactive-immune-response-17-december-2018/
 
Cinders66 said:
Pariante on radio on mental versus physical wasn’t helpful. Whilst psychiatric illness might have biological underpinnings it presents primarily as issues with mood and behaviour, physical illnesses primarily present with physical symptoms. Whilst dementia might sit in both courts arthritis is a physical illness not a mental one, so is MS , why is it with ME that suddenly all boundaries and classification is unacceptable when most pwME do not have major MH presentation.
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I find the key to understanding the debate is that although it looks like it's about classification of illness, it actually seems to be primarily about who gets the right (or burden) of treating patients with the illness in question. When viewed in this way, the debate begins making sense.
 
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Andy said:
Blog from the ME Association, can't say I'm particularly impressed with the part that I've bolded below.
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At a glance it looks like they have just copied the Kings College statement which they link to, and which is presumably the press release.
https://www.kcl.ac.uk/ioppn/news/re...e-syndrome-in-overactive-immune-response.aspx

Edit: This sentence appears in the Kings statement:
CFS, also known as myalgic encephalomyelitis (ME), is a long-term illness which is characterised by extreme tiredness
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Andy said:
Blog from the ME Association, can't say I'm particularly impressed with the part that I've bolded below.

https://www.meassociation.org.uk/20...-overactive-immune-response-17-december-2018/
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I interpreted this as a quote from the authors, rather than the view of the MEA, though that was not made clear making it read like a ringing endorsement of this study. I would have been much happier if they had made it clear that it was a quote and rather gave a cautious response given the problems with interpreting the study and the ludicrous over hype by the UK media.
 
I have not finished the paper, but let me say some things nice about it at my point of reading. It potentially shows that the intensity of the response is associated with later chronic fatigue. That is basically it. In ME research its best a footnote, and in CFS research it might be a whole sentence. For fatigue research, and only fatigue research, involving these pathways, it might be good.

Now its suggested from the Dubbo studies that intensity of the pathogen response is the best predictor of later chronic fatigue. So there might be something there. Its a long way to go from that to a model of ME ... a very very long way. Its a long way to go from there to even potential treatments, net alone deliverable, approved treatments.
 
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