Hornig/Lipkin cytokine study out now - press release

[Scarecrow]

I'm still puzzled about what this research means for long-term patients.

I'm thrilled at the evidence of something clearly, demonstrably wrong with our immune systems early in the illness, but I'm a little nervous that it's not clear what's going on later in the illness.

I don't think the take home message is that there is nothing wrong in the immune systems of long-term patients. Quite the opposite. Although they didn't find the same dysregulation in the cytokine network that was seen in the short-term patients, the investigators still noted that cytokine levels were lower in long-term patients than in controls, which they speculated on:

We were surprised to find that the levels of so many cytokines were higher in short-duration cases than in healthy controls. Equally surprising was the observation that these same cytokines were lower in long-duration cases than in healthy controls. We can only speculate as to why that might be. Possibly, as occurs with pancreatic β cell production of insulin in type 2 diabetes (42), or in chronic infections (43), the exuberant stimulation of cytokine-producing cells seen in the first 3 years of the illness leads to an “exhaustion” of the cytokine-producing cells thereafter. Although CD57, a marker of premature immune senescence that is found to increase in later phases of some chronic viral infections such as HIV (44) or hepatitis C virus (HCV) (45), has been shown to be decreased in previous work in ME/CFS (46, 47), studies that control for duration of illness may provide additional clarity as to the potential contribution of mechanisms of immune exhaustion to the immune changes observed later in the course of ME/CFS.

 

[Bob]

Sorry for what I know is a stupid question but what is the "Science Media Center" that I keep hearing about in lots of posts?

They were set up in the UK for the media to be able to approach scientific experts for quotes and explanations re scientific issues. There is a lot of controversy surrounding them generally as they tend to promote an establishment view of science rather than a range of informed views. But in terms of ME/CFS they were responsible for promoting misinformation in relation to the PACE trial which led, for example, to media headlines suggesting that 30% of patients 'recovered' after exercise etc. They promote the PACE trial literature from the point of view of the psych-lobby.

 

[SOC]

They were set up in the UK for the media to be able to approach scientific experts for quotes and explanations re scientific issues. There is a lot of controversy surrounding them generally as they tend to promote an establishment view of science rather than a selection of views. But in terms of ME/CFS they were responsible for promoting misinformation in reason to the PACE trial which led, for example, to media headlines suggestion that 30% of patients 'recovered' after exercise etc. They promote the PACE trial literature from the point of view of the psych-lobby.

It sounds like it was set up to make sure the "right" interpretation of scientific topics was given to the media. Very unscientific, and very dangerous.

 

[alex3619]

Interesting that they found lower cytokines in longer duration patients than in controls.

This pattern is one of the confounders that could have been preventing us from finding a biomarker (immune signature). ANY cohort was, immunologically, heterogeneous. No one marker would fit them all.

Why isn't C-Reactive Protein and/or sed rate elevated in short-duration patients if they have so much cytokine inflammation? Makes me wonder if maybe these two tests don't measure inflammation as effectively as has traditionally been thought

These are two of many markers. I haven't seen a list since I was at uni but its much longer than that. Its just these are two that are clinically useful in a wide range of conditions.

Some interesting tie-ins (ties-in?) to B cell maturation, which might support the autoimmune theory being explored in Norway and the UK.

Or autoinflammatory. This is additional evidence for an autoinflammatory state, and after three years for an exhausted autoinflammatory state.

 

[alex3619]

Anyone see anything from them suggesting avenues of treatment?

Hornig made a brief comment. Any cytokine network has the potential for many different treatments. They will have to identify and treat many of these cytokine issues to find out what works. Its very likely that this will initially be done in cell cultures from sick patients, based on what Klimas said in a recent video. That way huge numbers of drugs can be tested without risking patient health, before they move on to phase 1 human trials.

It is very likely that a drug cocktail will be the way to go if this research is right, and long and short term patients may get different treatments.

Please be aware that the research process may take more than five years, and without political will and funding might take much more.

 

[SDSue]

Please be aware that the research process may take more than five years, and without political will and funding might take much more.

Five years is too long. If the political climate changes, can this be sped up? If we get compassionate use status for things like Ritux, will that speed it up? C'mon Alex, give us some hope!

 

[alex3619]

replications on cytokines are not working in CFS

Which you would expect if this study is right. Why? Two different cytokine patterns mean any cohort that is not only for long term patients is a heterogeneous cohort.

It is right though that this will have to be independently replicated, and to move to a recognized diagnostic test the critics are right that formal studies of sensitivity and specificity will be required.

 

[alex3619]

If the political climate changes, can this be sped up?

NO. Five years is the MINIMUM for new treatments. It could be much longer. However, as Klimas recently discussed, older drugs (and hence cheaper) that are already approved, and have a great safety record, could be used off label after only phase 2 clinical trials. This reduces the timespan to only 3 years, but that is 3 years after the study starts. Adding startup times might mean the time frame is 4-6+ years, presuming of course that this research is robust.

It is the case though that particularly aggressive and daring doctors could start such treatments, off-label, very soon, for existing drugs. However there are no guarantees, and I doubt any insurance anywhere would cover it.

 

[Forbin]

Stuck in High Gear

The study supports the idea that ME/CFS may reflect an infectious “hit-and-run” event. Patients often report getting sick, sometimes from something as common as infectious mononucleosis (Epstein-Barr virus), and never fully recover. The new research suggests that these infections throw a wrench in the immune system’s ability to quiet itself after the acute infection, to return to a homeostatic balance; the immune response becomes like a car stuck in high gear. “It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,” says Dr. Hornig. “Early diagnosis may provide unique opportunities for treatment that likely differ from those that would be appropriate in later phases of the illness.”


http://www.mailman.columbia.edu/new...e-chronic-fatigue-syndrome-biological-illness

Although it could be solely a case of the immune system getting "stuck in high gear" (the exact phrase I used to describe my symptoms 30+ years ago), might it not be that there is something underneath "driving" the elevated cytokines? Even if the initial infection is a "hit-and-run" event, could that fleeting event trigger some other smoldering process that keeps the cytokines in high gear until the immune system becomes "exhausted" at the 3 year mark? The underlying process might then continue to make patients ill even after the cytokines cease to be elevated.

I guess my question is why are the cytokines stuck in high gear after any of what appear to be a wide variety of possible "hit-and-run" events? Maybe it's just genetic, but might this be where changes in the microbiome and/or an autoimmune response comes into play?

[I also have to admit to wondering whether it would be possible to temporarily induce this newly discovered cytokine profile by artificial means to see if doing so could briefly bring on ME/CFS symptoms in otherwise healthy individuals. Sort of like Barry Marshall swallowing a Petri dish of h. Pylori for science. Do I see any volunteers among the "it's all in their head" crowd in the audience?]

 

[alex3619]

The Science Media Center will be in full combat mode to attack the Lipkin's paper.

.. and more than a few of the psychobabble brigade, biopsychoSOCIAL proponents, and so on.

 

[SDSue]

[I also have to admit to wondering whether it would be possible to temporarily induce this newly discovered cytokine profile by artificial means to see if doing so could briefly bring on ME/CFS symptoms in otherwise healthy individuals. Sort of like Barry Marshall swallowing a Petri dish of h. Pylori for science. Do I see any volunteers among the "it's all in their head" crowd in the audience?]

I have a few "volunteers" in mind!

 

[alex3619]

I agree, it raises more questions than answers. On first blush, it's interesting to think about how many symptoms of ME are the same as those of certain cytokines administered in excess (fatigue, fevers, sickness behavior, tachycardia, cognitive dysfunction, etc.) but that doesn't explain why people sick > 3 years would continue to have these same symptoms if their cytokine levels drop below that of healthy people.

I think this is consistent with the activated microglia hypothesis. Three years of cytokine regulation may substantially alter their homeostatic set point and sensitivity to stimuli. After that even innocuous stimuli might trigger them. Please note that the cytokines in longer term patients may not be driving these issues. There are other patterns and networks. Also please note the speculative hypothesis that we have the same cytokine issues but the immune system is chronically exhausted and cannot express them.

 

[alex3619]

might it not be that there is something underneath "driving" the elevated cytokines?

Yes. This finding is about pathophysiology and is not yet evidence of causation.

 

[alex3619]

I have a few "volunteers" in mind!

Well, if I can make a list of those I would like to "volunteer" ....

 

[Sean]

They were set up in the UK for the media to be able to approach scientific experts for quotes and explanations re scientific issues. There is a lot of controversy surrounding them generally as they tend to promote an establishment view of science rather than a selection of views. But in terms of ME/CFS they were responsible for promoting misinformation in relation to the PACE trial which led, for example, to media headlines suggesting that 30% of patients 'recovered' after exercise etc. They promote the PACE trial literature from the point of view of the psych-lobby.

As far as PACE and ME/CFS generally, the SMC is nothing more than a propaganda vehicle for certain vested interests, IMHO.

The fact that Wessely is their advisor on these matters says it all. Such a blatant conflict of interest should be a massive warning flag to any supposedly science based organisation.

Should be.

 

[Aurator]

Message to Messrs. Wessely, Sharpe et al.:

Great news! In a matter of minutes a handful of biologists have just done more for the psychological health of countless ME patients than thousands of trained psychiatrists delivering thousands of hours of CBT.
Your dealings with ME have clearly not been a happy experience for you. It might be useful to go over how you got involved with the illness in the first place. If it's alright with you, we could go back to your early childhood and start there. Would that be OK? Mm?

 

[Gingergrrl]

Thank you to everyone who explained to me what the SMC is and I get it now. What a joke and crock of BS.

@alex3619 You were mentioning possible cytokine treatments in this thread and I was wondering if something like Valcyte would be considered a cytokine treatment? And also wondering what other treatments might fall into this category? Thank you in advance!

 

[alex3619]

@alex3619 You were mentioning possible cytokine treatments in this thread and I was wondering if something like Valcyte would be considered a cytokine treatment? And also wondering what other treatments might fall into this category? Thank you in advance!

I wont know without doing some investigating. I suspect this might include biological drugs, that is things like antibodies, but there are lots of drugs that have been discussed over the years for this kind of thing. There are a wide range of cytokines involved, and this means we have many targets. With many targets comes many drugs, and potential drugs, and drugs overllooked by pharma because they didn't see a need for them.

If this study is replicated then you might see Pharma finally getting involved, but only for new or newer drugs. Repurposing old drugs will have to be researched with other funding.

Let me say again that this will probably require a drug combination, which may be why it has been so hard to find by chance. Also, the initial targets may be critical factors found in the cytokine network.

Whether this treatment will have any impact on long term patients is less certain. If immune exhaustion is the key then it might. If activated microglia is the key, then other treatments may be necessary, either on their own or in combination with the anti-cytokine treatments.

 

[SilverbladeTE]

SMC = the Establishment/Corporate mouthpiece

as I've said elsewhere, the UK and the USA are really run by vile webs of nepotism and very powerful, malign sons of bitches, from corporations, to small elite family groups you will find often sitting on the boards and committees of many ventures and government bodies.
Modern day Corporate Fascism.

Opposite extremes are just as bad as each other, the problem though is that unlike with Stalin, we don't have an obvious "Big Bad Evil Guy" to alert folk, rather it's a dark cloud of corruption that stupefies and misleads, like fighting fog.
A deliberate design form that is the evolution of corruption in Western democratic Capitalism which has emerged to destroy the very thing that gave it birth as it's absolutely antithical to Democracy and Capitalism.

So, if you get yourself or spouse for example, onto the committee overseeing the regulation of the corporation you are the CEO of, you can rig both sides of the game and that is EXACTLY what happens.
Note the recent exposure of two former British Ministers of Defence taking cash for political influence for private companies.

Thus corproates etc sponsor mouthpieces like the SMC to alter Public opinion, spreading their propaganda and lulling folk asleep, to ignore the "little man behind the curtain", or the protestors on the streets.

We are actually living in a form of "1984" that Orwell couldn't have written out as brilliantly effective and diabolic.
Stalin killed vast majority of his victims by deliberate or arrogant uncaring stupidity causing famines.
Likewise, price fixing of food and oil, demanding farmers use seeds that can't propagate themselves (see Monsanto) have lead to megadeaths from artificial famines in recent years because poor folk can't afford the obscene prices....but few have spoken up about this as it's not obvious when there isn't the NKVD "neck shooting" dissenters and of course, when the corporates own the bloody media so don't report it!

 

[zzz]

Cort Johnson also has an excellent analysis of this study in the article The Clock Was (Is) Ticking: Major Study Suggests ME/CFS is Hit and Run Disorder over at Health Rising. Cort discusses one aspect of the study that has not received much attention: What drives this illness once the immune activation has died down? Here's what he reports:

Hit and Run

That suggests the disease has in some way moved on from the immune system. The authors of the paper didn’t have a great explanation for why people remained ill after their immune system activation had died down or had become decreased. If Younger’s findings pan out perhaps the lone elevated immune marker – leptin – found is enough.


The findings suggested ME/CFS is a hit and run disease.

An email to Jarred Younger gave a quick answer, warning that it was not based on a close reading of the paper. He suggested systemic inflammation may drive ME/CFS early on but sensitized microglia and astrocytes in the central nervous system drive it in its later stages. Because we don’t have good ways to test central nervous system inflammation at that point the disease mostly becomes invisible to testing afterwards.

So for those of us who have been ill longer than a few years, the central problem appears to be in the brain and spinal cord, and treatments that address central nervous system dysfunction would seem to hold the most effective promise if this is true.

@alex3619 You were mentioning possible cytokine treatments in this thread and I was wondering if something like Valcyte would be considered a cytokine treatment? And also wondering what other treatments might fall into this category? Thank you in advance!

I'll agree with Alex, but I'll elaborate a bit. Right now, I don't know of any evidence that Valcyte is effective against cytokines. But there is some evidence, such as reported by Dr. Montoya and experienced by you, me, and many others, that Valcyte has a direct effect on the central nervous system, and can help heal sensitized microglia. Basically, what we've experienced is a desensitization of at least some of the hypersensitized parts of the central nervous system, and for many people, this then has systemic effects. This makes a lot of sense based on the explanation above by Jarred Younger.

Interestingly, there is an article in this month's Scientific American (the March issue) that talks about recent discoveries that further connect the central nervous system with the immune system. The article is entitle "Shock Medicine" and is primarily about using electrical stimulation on various nerves, specifically the vagus nerve, for medical purposes. The following brief quote from the article sums up the author's findings:

Searching the published literature turned up evidence that the major organs of the immune system, including the thymus, spleen, liver, lymph nodes and lungs, are all innervated with connections that descend from the brain. But none of this work identified reflex circuits controlling immunity. In fact, the antithesis had become medical dogma. Decades of immunology had focused on the role of the immune system in protecting the body independent of the nervous system. Immunity, in these accounts, centered on the workings of lymphocytes, monocytes, macrophages, and other white blood cells, but not on neurons.

The inflammatory reflex, which keeps the immune system from becoming overactive or underactive, is the name I gave the circuit that prevents toxicity and tissue damage.

[Bolding mine.] So this article cites evidence of two-way communication between the nervous system and the immune system to an extent not observed before. This would help explain why even when the initial problems with the immune system subside, problems with the central nervous system can cause immune dysfunction to continue. Much more research is obviously needed. But if indeed the locus of this illness moves from the immune system to the central nervous system, then in later years, treatments directed at the central nervous system would seem to be the best way to get at the root of the problem. (Of course, this doesn't exclude other treatments where indicated.)