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

Not sure whether this is really relevant, but the reference to kynurenine looked interesting. NB participants include some dodgy people, e.g. Trudie Chalder.

Source: University of Essex (or Sussex?)

Date: November 29, 2018

URL: http://sro.sussex.ac.uk/80506/

Persistent fatigue induced by interferon-alpha: A novel, inflammation-based, proxy model of Chronic Fatigue Syndrome
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Russell, Alice, Hepgul, Nilay, Nikkheslat, Naghmeh, Borsini, Alessandra, Zajkowska, Zuzanna, Moll, Natalie, Forton, Daniel, Agarwal, Kosh, Chalder, Trudie, Mondelli, Valeria, Hotopf, Matthew, Cleare, Anthony, Murphy, Gabrielle, Foster, Graham, Wong, Terry, Schutze, Gregor A, Schwartz, Markus J, Harrison, Neil, Zunszain, Patricia A and Pariate, Carmine M

- Brighton and Sussex Medical School, University of Essex, U.K.

Abstract

The role of immune or infective triggers in the pathogenesis of Chronic Fatigue Syndrome (CFS) is not yet fully understood. Barriers to obtaining immune measures at baseline (i.e., before the trigger) in CFS and post-infective fatigue model cohorts have prevented the study of pre-existing immune dysfunction and subsequent immune changes in response to the trigger.

This study presents interferon-alpha (IFN-alpha)-induced persistent fatigue as a model of CFS.

IFN-alpha, which is used in the treatment of chronic Hepatitis C Virus (HCV) infection, induces a persistent fatigue in some individuals, which does not abate post-treatment, that is, once there is no longer immune activation. This model allows for the assessment of patients before and during exposure to the immune trigger, and afterwards when the original trigger is no longer present.

Fifty-five patients undergoing IFN-alpha treatment for chronic HCV were assessed at baseline, during the 6-12 months of IFN-alpha treatment, and at six-months post-treatment. Measures of fatigue, cytokines and kynurenine pathway metabolites were obtained. Fifty-four CFS patients and 57 healthy volunteers completed the same measures at a one-off assessment, which were compared with post-treatment follow-up measures from the HCV patients.

Eighteen patients undergoing IFN-alpha treatment (33%) were subsequently defined as having 'persistent fatigue' (the proposed model for CFS), if their levels of fatigue were higher six-months post-treatment than at baseline; the other 67% were considered 'resolved fatigue'.

Patients who went on to develop persistent fatigue experienced a greater increase in fatigue symptoms over the first four weeks of IFN-alpha, compared with patients who did not (Delta Treatment Week (TW)-0 vs. TW4; PF: 7.1p/m1.5 vs. RF: 4.0p/m0.8, p=0.046). Moreover, there was a trend towards increased baseline interleukin (IL)-6, and significantly higher baseline IL-10 levels, as well as higher levels of these cytokines in response to IFN-alpha treatment, alongside concurrent increases in fatigue. Levels increased to more than double those of the other patients by Treatment Week (TW)4 (p=0.011 for IL-6 and p=0.001 for IL-10). There was no evidence of an association between persistent fatigue and peripheral
inflammation six-months post-treatment, nor did we observe peripheral inflammation in the CFS cohort. While there were changes in kynurenine metabolites in response to IFN-alpha, there was no association with persistent fatigue. CFS patients had lower levels of the ratio of kynurenine to tryptophan and 3-hydroxykynurenine than controls.

Future studies are needed to elucidate the mechanisms behind the initial exaggerated response of the immune system in those who go on to experience persistent fatigue even if the immune trigger is no longer present, and the change from acute to chronic fatigue in the absence of continued peripheral immune activation.

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(c) 2018 University of Essex

 

They keep referring to " peripheral immune activation" ,so presumably ongoing neuroinflammation could be present which could only be measured by scans?

 

My money's on all the BPS lot riding the coattails of others biological research and then proclaiming themselves our saviours.

It's one thing to have been mistaken. That can happen to anyone. It's quite another to have done so much harm to so many while ignoring all the info that comes your way until you can't any longer.

They will not get what I consider just. When you get caught up in our situation you get to see how unjust things can be.

 

Fact laundering via the spin cycle.

I find I keep wondering how my opinions would be more generous if I wasn't so affected by the horrible plague of this illness and seeing all of the other suffering. But there is no going back on what you know except for people who can see a clear upside to ignorance because it benefits them.

What they have done and probably will do happens all the time in different ways all round the world. But it's a bitter pill to swallow all the same.

I periodically see people write 'but it's 2018' or something like. It has no relevance. The specifics may change but the overall tone is that some people need to find extraordinary power over others and will do whatever that entails and others will be seen as weak minded/willed by virtue of simply falling ill. The idea that the vulnerable may have insight into the situation and the capacity to contribute would offend their sense of who's in charge here.

Different century -- same humans.

 

Merged thread

Tom Feilden just posted:

https://twitter.com/user/status/1074411178175197185

 

Could this possibly be the beginning of a phased climb down?

 

Let's hope this can be trusted, given KingsIoPPN => Kings Institute of Psychiatry, Psychology & Neuroscience.

 

Hmm, "underlying causes", which could very well mean, "wellll, it starts with an overactive immune response, but then it's the unhelpful beliefs of the patient that perpetuate it". As always, the devil will be in the detail.

 

Yes, the BPS folk have never denied a potential physiological initial trigger condition. What will really count is what this research deems the perpetuating factors to be down to, which they have always said is down to unhelpful illness beliefs, blah blah.

 

can anyone say more, without breaking the embargo?!

 

I'm going to go out on a limb and guess that even if the research proves to be well done that the investigators will then take the opportunity to over interpret what exactly the data is telling them. If not in the actual research conclusions then in the press afterward (which they will tell you they have no control over).

I don't think they are willing to give up on their completely made up version of whatever they think this illness is. They know they can't go back to the old paradigm but that won't stop them from conjuring a new one.

And yes, it could turn out to be some sort of hybrid concept that gives some concession to what is now beyond denial but I'd be very surprised if there is anything like a conclusion that we can't be fixed with a few BPS style party tricks.

 

The "Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of Chronic Fatigue Syndrome" study? If so we have this thread on it, as well as at least one more that I can't find at the moment, https://www.s4me.info/threads/uk-cmrc-conference-2018-prof-carmine-pariante.6096/

 

Someone with the ability to do so will have to check if the Abstract and the rest of the paper are describing the same research. They don't always coincide.

 

I hope that if any patient groups are asked to comment they don't join in with over enthusiastically hyping this research. @Action for M.E. @Russell Fleming (Is Russe;l the best person to tag for MEA? I couldn't find another). I'm sure that there often is a view that it's worth trying to sound excited/positive when speaking on the BBC about any potentially useful finding, but there are a lot of reasons why it would be wise to avoid doing so.

 

That sounds like what he presented at CMRC, or certainly a variation of it.

 

There have been other studies looking at the effects of interferon-alpha and fatigue:
https://www.ncbi.nlm.nih.gov/pubmed/?term=interferon-α+fatigue

The CDC CFS budget was even used to support a study in the US in the 2000s.

I wonder whether different studies found different or similar findings.