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

Andy said:
According to this, https://gtr.ukri.org/projects?ref=MR/J002739/1, which would appear to be the, I'm assuming, funded application for this study and from my skim read it would seem that all the claims made recently are all in line with the original application. So my question is why was a study on chronic fatigue funded with funds meant for CFS? And the obvious answer is that, at the time, and seemingly currently as well, the two things are synonymous to the research team and the funding body.
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I think it was justified to try to make use of funding for CFS to look at the side effects of interferon alpha, as that provided a convenient sample of people they could look at in a controlled way.

Ideally they'd be able to do this sort of research on those coming down with something like EBV, but that would be extremely difficult to do as we don't know when people are going to come down with that (assuming we're not infecting people for the sake of our experiment).

I think that the basic idea of the experiment was fine and potentially interesting (although longer follow up was really needed), but then their weak results from a small sample of questionable relevance to CFS were hugely over-hyped.
 
Esther12 said:
Ideally they'd be able to do this sort of research on those coming down with something like EBV, but that would be extremely difficult to do as we don't know when people are going to come down with that (assuming we're not infecting people for the sake of our experiment).
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That is why you recruit large numbers in a prospective study, such as the Dubbo study. You then track them for years.
 
Suffolkres said:
"......They suggest that some people who are depressed may actually
be suffering from an over-heated immune system........"

I wonder what this 201 article brings to this thread. i have the magasine somewhere....

https://www.newscientist.com/article/mg17022954-600-a-mind-under-siege/

"16 June 2001

A mind under siege
By Phyllida Brown

A FIFTY-year-old woman living in Japan is infected with a potentially fatal
virus, hepatitis C. Doctors bombard her body with a powerful drug to boost her
immune response. The drug beats back the virus, but has horrific side effects.
She becomes inexplicably moody, rapidly sinking into a depression so savage that
the woman douses herself in oil and sets herself alight.

Fortunately, her suicide attempt fails and she recovers fully. But the
woman’s terrifying experience is not unique. Over the past few years, there’s
been a steady trickle of bizarre reports of people becoming suicidal after
taking alpha interferon and interleukin-2, two popular immune-boosting drugs.
Hundreds of others have become seriously depressed.

But here’s the rub. Patients and doctors are not rounding on the makers of
these drugs. Instead, everyone tends to think the psychological side effects are
a price worth paying for drugs that can combat cancer, hepatitis and other
life-threatening infections. Indeed even the terrible suicidal urges themselves
are now turning out to have a silver lining. They are awakening interest in one
of the most promising new avenues in depression research since Prozac left the
labs.

Most of us associate depression with being run down and having poor immunity
to infections. The startling side effects of the immune-boosting drugs turn that
notion on its head. They suggest that some people who are depressed may actually
be suffering from an over-heated immune system, and that damping down
inflammation could offer a brand new way to treat routine clinical
depression—while making billions for the pharmaceuticals industry into the
bargain. It’s a theory that recasts depression—one … ( subscription)
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And look what Pariante says on his Twitter profile: 'I want to know why stress makes us ill, and how to get better.'

He's doing this research because he wants to show stress damages the immune system and causes a physical illness, namely 'CFS'. And KCL are backing him because they will then treat the illness with CBT and GET to restore the immune system, reversing the stress damage. For the BPS crowd it's always been about the interplay between psychology and physiology. His is just a more complex version.


ETA: to tidy up some grammar.
 

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strategist said:
The UK scientific establishment may be incapable of seriously investigating ME/CFS as long as CBT/GET lobby has so much influence.

For example, in this study one can see the conflation of single symptom with a syndrome. This is something that originated from the CBT/GET lobby and the result is that the study tells us nothing about ME/CFS. Presumably Pariante it just aligning himself with local expert opinion and that means CFS is viewed as substantially equivalent to persistent fatigue (no matter how mild).
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Yes, and in the interview, he responded to my mention of the multi-systemic nature of ME by claiming the immune system can cause multi-systemic changes, including the brain and the liver.
 
Neuroscience News
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.
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https://neurosciencenews.com/chronic-fatigue-immune-10371/

 
Good summary from MEAction: - Post-interferon fatigue study - a mixed bag

In general, this is a small study that may have interesting implications for post-viral chronic fatigue. While the study has aspects that are potentially interesting, it ends up comparing (possibly) IFN-α-induced fatigue, but possibly garden-variety post-infectious fatigue, to Oxford CFS; and since Oxford CFS is such a broad category, it has the potential to include individuals with the same etiology in the pIFNF group. It would have been interesting to see their pIFNF group compared to a group that experiences PEM.

Finally, while the measurements are objective, the study says nothing about ‘perpetuating factors’. Many psychosocial theorists support an infectious or immune trigger for ME but state that psychological factors then perpetuate the disease, or that despite infectious and immune triggers, CBT and graded exercise remain the best possible treatments. Considering some of the authors of this paper subscribe to this paradigm, the next logical step for them would be to attempt to show a connection between psychosocial theories and the results presented here.

Even so, given that IL-6 and IL-10 dysregulation are so common in the ME literature, the researchers may have dropped a few breadcrumbs for those with a biomedical bent to follow. And let’s not forget that the paper shows childhood trauma is no more common in people who do develop long-standing fatigue than in those who do not. This is a win for those patients who’ve been told to heal emotional trauma in order to recover their physical well-being.
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There are some pretty bold statements in that ScienceAlert article:

"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," says Alice Russell, a psychiatrist who researches CFS at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN).

"Our findings suggest that people who have an exaggerated immune response to a trigger may be more at risk of developing CFS."
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"In conclusion, findings from this study support the hypothesis that abnormal immune mechanisms are important in CFS, but only early in the course of the illness, around the time of the trigger, rather than when the syndrome is established," the authors conclude.

"Moreover, our study confirms the importance of the acute fatigue response to the trigger, rather than of the recovery period preceding the illness."
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"A better understanding of the biology underlying the development of CFS is needed to help patients suffering with this debilitating condition," says co-author Carmine Pariante, an expert in biological psychiatry at King's College.

"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."
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fossil said:
ike they seem to be suggesting in this paper?

Depression and anxiety in patients receiving interferon-alpha - The role of illness perceptions.

Hepgul N, et al. J Health Psychol. 2018.

Authors
Hepgul N1, Pariante CM1, Baraldi S1, Borsini A1, Bufalino C1, Russell A1, Agarwal K2, Cleare AJ1, Forton DM3, Henderson M1,2, Mondelli V1, Ranjith G4, Hotopf M1.
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Oh dear.

Sad, but not exactly shocking.
 
Jonathan Edwards said:
I think the confusion is that a slug of interferon tends to mimic what happens in an acute infection such as flu when the body produces its own slug of interferons. Hep C very often produces silent disease for months or years.

I agree that the idea that subjects with worse fatigue have more active immune responses seems wrong. In flu the immune response is the production of interferon. But in this study the interferon comes from outside. What seems to be different about those with more symptoms is that they are more sensitive to an immune mediator.

As far as I know none of the people involved are actually immunologists and the immunological analysis in general seems pretty simplistic.

What the study might be telling us is that some people's nervous system, or physiology as a whole, is more susceptible to a permanent regulatory resetting by an 'immunological storm'. Immunological storms are known to be capable of producing ill effects. The trial of a T cell stimulant at Northwick Park caused serious harm by releasing cytokines. TNF alpha in too high a dose can worsen mortality from infection. But the susceptibility would lie in receptor-mediated sensitivity rather than 'overactivity' in all these cases.
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My brother was having Hep C interferon treatment at the very time of my severe ME onset, same year. His exhaustion sounded similar to mine. I had full-blown ME (in a huge and overwhelming immunological storm) that would not dissipate. It took a good two years for that immunological storm to abate. I would never want to experience anything like that again. Very frightening to feel your immune system in such a volatile state.

Sorry I have only been able to skim some posts.
 
Lucibee said:
As far as I understand it, they were looking at a group who had a high risk of developing chronic (or persisting) fatigue - not CFS per se.
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Yes.

Lucibee said:
These patients had already had a very strong viral infection (HCV), which is why they were being treated with IFN-alfa at all, so to claim that they were looking at what happens early on in the infection is not true. These were patients with a known persistent viral infection who were undergoing therapeutic immune challenge.
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That's a considerable omission. What we're looking at, then, is people with a strong immune response to viruses or with a particularly severe viral infection and commensurate response.

Lucibee said:
Or is it more an indicator of the severity of the infection?
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Yes, maybe. Or perhaps what they have is a functional but sluggish immune response, such that when it finally 'kicks in', the response is pretty nuclear.

If only we had better research into genetics.
 
Esther12 said:
Yes, but we still don't get biological measures of immune response immediately as infection begins.
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That is a logistical problem that can be solved. Its possible to track this within twenty four hours if you are prepared, but that would mean pre-existing responses set up, and that costs even more money. These issues are fixable, but the better the fix the more expensive it is, and therefore the harder it is to sell to grant bodies.
 
If this is a repeat, I apologise!

From LocalME;


https://steamtraen.blogspot.com/2018/12/have-scientists-found-explanation-for.html

"Thanks for posting that link V.
Prof Pariante did not make clear that this study was not about ME, but Jon Peters was very good and he pointed this out. He was also very good at pointing out there is a lot of other research finding biomedical abnormalities.

I haven't read the study myself, but there is a critique of the study in a blog article by Nick Brown, link below. The SMC was behind the publicity (who'd have guessed?)."


Some excerpts from Nick Brown's article:

"I was allowed in without a press pass after identifying myself as a researcher, but when I tried to get clarification of a point that had been made during the presentation I was told that only reporters (i.e., not researchers or other members of the public) were allowed to ask questions."

"There are many possible causes of fatigue, and I don't think that the authors have given us any good reason to believe that the fatigue that was reported by their hepatitis C patients six months after finishing an exhausting medical procedure that itself lasted for half a year or more was caused by the same mechanism (whatever that might be) as the multi-year ongoing fatigue in ME/CFS patients, especially since, for all we know, some or all of the 18 cases of persistent fatigue might have been only marginal (i.e., a small amount worse than baseline) or resolved themselves within not too many months."

"None of the eight-week or 12-week results appear in the article, and the two from the end of treatment are extremely unconvincingly argued (see previous paragraph). It is possible that the authors simply did not perform any tests on these results, but I am inclined to believe that they did run these tests and found not to provide support for their hypotheses."

"I don't find Russell et al.'s study to be very convincing. My guess is that different cytokine levels do not predict fatigue in either hepatitis C/IFN-α patients or ME/CFS patients, and that the purported relation between cytokine levels at four weeks into the IFN-α treatment and subsequent fatigue may well just be noise. In terms of explaining how ME/CFS begins, let alone how we might prevent or cure it, this study may not get us any closer to the truth."
 
Suffolkres said:
If this is a repeat, I apologise!

From LocalME;


https://steamtraen.blogspot.com/2018/12/have-scientists-found-explanation-for.html

"Thanks for posting that link V.
Prof Pariante did not make clear that this study was not about ME, but Jon Peters was very good and he pointed this out. He was also very good at pointing out there is a lot of other research finding biomedical abnormalities.

I haven't read the study myself, but there is a critique of the study in a blog article by Nick Brown, link below. The SMC was behind the publicity (who'd have guessed?)."


Some excerpts from Nick Brown's article:

"I was allowed in without a press pass after identifying myself as a researcher, but when I tried to get clarification of a point that had been made during the presentation I was told that only reporters (i.e., not researchers or other members of the public) were allowed to ask questions."

"There are many possible causes of fatigue, and I don't think that the authors have given us any good reason to believe that the fatigue that was reported by their hepatitis C patients six months after finishing an exhausting medical procedure that itself lasted for half a year or more was caused by the same mechanism (whatever that might be) as the multi-year ongoing fatigue in ME/CFS patients, especially since, for all we know, some or all of the 18 cases of persistent fatigue might have been only marginal (i.e., a small amount worse than baseline) or resolved themselves within not too many months."

"None of the eight-week or 12-week results appear in the article, and the two from the end of treatment are extremely unconvincingly argued (see previous paragraph). It is possible that the authors simply did not perform any tests on these results, but I am inclined to believe that they did run these tests and found not to provide support for their hypotheses."

"I don't find Russell et al.'s study to be very convincing. My guess is that different cytokine levels do not predict fatigue in either hepatitis C/IFN-α patients or ME/CFS patients, and that the purported relation between cytokine levels at four weeks into the IFN-α treatment and subsequent fatigue may well just be noise. In terms of explaining how ME/CFS begins, let alone how we might prevent or cure it, this study may not get us any closer to the truth."
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Yup, shared in this thread already and Nick Brown has posted a couple of times as well.
 
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