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TH2 Immune System Dominance and Heterogeneity in ME/CFS

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Th2 Immune System Question

Hoping Marco is still out there. I am just reading this and was about to start HGH for CFS/ME. I
have been thru identical series of events. Are you saying that HGH is safe and a good option for our "over active immune" systems...?? I didn't understand how "helping" our Immune System with HGH would not be a dangerous situation.... If we are 'over active", and we "boost" our Immune System, is that not counterproductive and/or harmful???


I appreciate that, as set out, this is all very simplistic, but I feel that it represents a much more satisfactory paradigm than the current search for the 'magic bullet' and discussion of sub-sets and heterogeneity. All those with ME/CFS have an immune dysfunction. They only differ on the trigger and duration of illness. The Broderick et al paper, which states that the difference between the structure of cytokine expression in the CFS/ME group compared to the control group is ten times the magnitude of the variability within the groups certainly suggests that there may be a unique pattern of immune dysregulation.

What role for XMRV?

XMRV may turn out to be a causal factor in many cases of ME/CFS, may be another opportunistic infection or it may either be THE virus (and detection just needs to be improved) or THE factor which predisposes us to develop ME/CFS when presented with another triggering event. Certainly an explanation is needed as to why some people develop TH2 dominance and others don't when faced with vaccinations, viruses or other triggering events.

As for CBT/GET and the Gupta Programme and similar. Perhaps they have some benefit for those diagnosed as CFS but who are either no viral load and not TH2 dominant (i.e. they don't have ME:CFS) or those with no viral load but who are TH2 dominant (non viral onset) but at an early stage of illness and have neither acquired opportunistic infections nor HGH depletion. Both 'therapies' might help rebalance the immune system to some extent (or in the case of GET might exacerbate the problem) but neither will treat active virus infections.


CASE STUDY

Well what about me?

Although circumstances might suggest contact with an enterovirus, I have never been tested for viruses and have no evidence of any present or past viral infection.

Onset was sudden (full health to poor health) but not all of the symptoms were there at the start. My state of health has undergone three distinct step changes downwards over the course of coming up to 25 years.

I had developed GI problems and anxiety/depression and then collapsed while training. Since then I haven't been able to tolerate any aerobic exercise.

I then developed dizziness on standing, extreme sensitivity to cold, a wide range of food and chemical intolerances, joint and muscle pains, headaches etc but fatigue as such was not a major issue and I was able to even combine full time working and part time study so no cognitive issues.

Prior to the onset of illness though I was probably overactive physically, undernourished and under some personal and academic stress.

To fit it into my suggested schema; I was probably pushed to a TH2 dominant immune response but with no or a low viral load. TH2 dominance would explain the IBS, new intolerances and possible joint and muscle pains. PEM etc I don't know possibly de Meirleir's channelopathy.

Next step change I suddenly developed a whole raft of new symptoms in addition to those existing. These included rapid unexplained weight gain (abdominally for the first time) loss of strength and muscle tone, rapid greying of hair and apparent ageing, insomnia, anxiety, exacerbated fatigue, profuse sweating, dry skin etc. Strangely enough I have never again experienced real depression since this date. All very suggestive of exhausted HGH. Again circumstances might suggest another enterovirus effect (or vaccine?) as both step changes followed shortly after holidays abroad.

Finally, after seven years I had to leave work (for the afternoon I thought) and never went back. To the existing symptoms I added extreme fatigue (needing to sleep during the day) and severe cognitive problems. For the first number of months I couldn't walk, think, read or drive and still can't when I have a frequent bad spell.

I can't identify any specific triggers for the last step change. Perhaps this last stage was viral or perhaps I carried on too long with no relief? Perhaps the last stage was me developing full blown ME and not just part of it?

Any thoughts/criticisms would be much appreciated.
 

Marco

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Hi donnawhit.

I'd forgotten about this thread.:D

First let me reiterate that I have no specific expertise - just putting things together from what I've read in a way that makes sense to me.

For what its worth, the concensus seems to be that our immune systems are deregulated rather than overactive globally with the pro-inflammatory TH2 side over-expressed and the anti-viral TH1 side under-expressed or underactive. Very generally.

Under this scenario (nicked from Cheney and others) our immune systems constantly pump out RNaseL to compensate for the reduced and ineffective anti-viral immune response and in doing so eventually exhaust our HGH reserves which is needed to produce RNaseL. Low HGH is associated with its own range of symptoms which include the types of diffuse aches and pains, muscle weaknesses etc we experience.

Low HGH is therefore a consequence of the immune dysregulation and not the cause.

HGH supplementation would therefore allieviate some of these additional symptoms but would not necessarily restore the immune balance.

From a VERY cursory google search I've seen articles that describe the effects of HGH supplementation on the immune system as a modulator (i.e. that restores any TH1/TH2 imbalance) as a TH1 booster and in some cases as raising TH2 levels (possibly a foreign substance rejection type response).

I'll hold my hands up a say I just don't know.

However low HGH has been frequently found in ME/CFS, usually perceived as resulting from disrupted sleep patterns rather than as a result of an immune dysfunction and is often suggested for ME/CFS.
In fact forum members' experiences of HGH supplementation is discussed on this thread and is a better guide than I can offer :

http://www.forums.aboutmecfs.org/showthread.php?7864-Human-Growth-Hormone

As long as you are taking it under the care of a good physician I doubt there would be any problem and should you notice a sudden increase in inflammatory type symptoms then you can reconsider if any benefits outweigh the downsides.

Hope this helps a little.
 

richvank

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Hi, Marco.

Another possibility to explain the low hGH in ME/CFS might be glutathione depletion in the hypothalamus and pituitary.
hGH is one of the hormones that is a secretory protein containing cystine disulfide bonds. This class of secretory proteins is vulnerable to glutathione depletion in the cells that synthesize them, because glutathione is necessary to keep the cysteine in its reduced state until after the amino acid chain has been formed and has entered the endoplasmic reticulum in these cells, where the disulfide bonds are supposed to be formed.

This hypothesis can explain the deficits or deregulation of several other secretory proteins in ME/CFS as well, including ACTH, antidiuretic hormone, perforin, and oxytocin. The depletion of glutathione can also explain many other aspects of this disorder, including the buildup of toxins and the shift of the immune system to Th2. More info on the GD-MCB hypothesis is available at www.cfsresearch.org by clicking on CFS/M.E. and then on my name.

Best regards,

Rich
 
C

Cloud

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I'm glad to see this thread resurrected. The very first GP who diagnosed me with CFS 16 years ago (when we still had very little understanding of the immune dysfunction in CFS), said he based my diagnosis primarily on an up-regulated TH2. He put me on IP6, Transfer Factor, LDN, and GI support. So, while the idea of the TH2 up-regulation is not news, I do agree with Marco that this particular Immune shift may be the one true consistent finding that can be used as a bio-marker for diagnosis and treatment of CFS (apologies if misunderstood Marco). Plus, we have more understanding of potential cause, effect, and treatment now. It surely has opened up a conversation with insightful ideas unheard of just a few years ago. Very interesting topic....thanks everyone!
 

Marco

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There was a short piece one the BBC today where a first Gulf War survivor was talking about plight of the Gulf War Syndrome sufferers, 20 years on.

This prompted a little googling and brought up this explanation for how multiple vaccines may have contributed.

Nothing new here but very clear and easily understood :

Dr. Philip F. Incao of Denver, Colorado provides what may be an explanation of why some people given this cocktail of vaccinations remained healthy while the health of others was sent into decline resulting in chronic illness. Dr. Incao explains that the immune system and mechanism by which vaccinations work, is much more complicated than was thought until recently. Rather than stimulating the whole immune system against a certain pathogen, vaccinations only stimulate the humoral, or Th2, branch of the immune system which is responsible for producing antibodies that recognize pathogens as invaders. Over activation of the Th2 mediated immune response leads to allergic and autoimmune disease. Dr. Incao suggests that giving vaccinations to people whose immune systems are already Th2 dominant will exacerbate exiting conditions and may lead to what we know as Gulf war syndrome. A large body of research seems to confirm this, showing that those veterans with gulf war syndrome tend to have an immune system shifted towards a Th2 response (17, 18, 19).
Read a full explanation from Dr. Incao

How vaccinations work

http://www.ei-resource.org/articles/gulf-war-syndrome-articles/how-vaccinations-work/
 

Enid

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Phew - hard going with you guys on the science, but well worth the read. Maybe we will put all together and suss out.
 

sela

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HGH supply becomes exhausted.

Low HGH levels have been associated with : Low energy, decreased lean muscle mass, increased abdominal fat, decreased strength and exercise tolerance, feelings or anxiety sadness and social avoidance, dry thin skin, sleep disturbances, decline in bone density, raised cholesterol, low blood sugar, irritability, night sweats etc.


what about trying hgh? at least diagnostically. also what about ldn?
 
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T2 helper dominance

I am sorry if I have missed this in the posts but does anyone know why it is you can feel better with a cold or temporarily a day or 2 after a cold when suffering severe ME/CFS. I don't really get viruses, sometimes I get an inkling there may be one in the mix but it is hard to tell the difference. I definitely believe TH2 dominance is significant in the ME/CFS puzzle causing a total immune overreaction to things we are exposed to on a daily basis. Thanks for the information on here.
 
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This is a good thread - I think most of the hypothesis presented here will prove to be correct. It seems to be an imbalance with TH2 dominance. I have been making good progress on LDN and can exercise now again without triggering the PEM/PENE storm lasting for days/weeks, however I still have an inflammatory overreaction to moderate/strenuous exercise which usually kicks in within 12 hours and lasts around 24-48 hours.
 

Hip

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It you look at the work of Dr John Chia, where he uses oxymatrine in CFS patients to try to swing the Th1Th2 balance back to Th1, he noted that although oxymatrine works for around 25% of CFS patients, and for these lucky patients the immune system does move towards Th1, as soon as you stop taking oxymatrine, he found that the immune system swings right back to Th2, as "if it were spring-loaded", as Chia comments.

So as Marco suggests, there may be factors present in CFS patients that are constantly forcing the immune system over to Th2, making it impossible to properly clear viral infections.

And although CFS patients may try taking immunomodulators that can shift the immune response to Th1, such as oxymatrine (and also Imunovir, and many others), they are fighting an opposing force in their bodies, perpetually pushing the immune system over to Th2. So this makes it very hard for the Th2 to Th1 immunomodulators to do their job, as they may not be able to overcome this opposing Th2 force.

I have been interested in this idea of factors present in CFS patients that are constantly forcing the immune system over to Th2 for a while now, and I am beginning to collect information on factors that do push the immune system to Th2.

One such factor is the bacterial toxin LPS (lipopolysaccharide) from Gram-negative bacteria, which forces the immune system over to Th2. So let's say you have some gut overgrowth with Gram-negative bacteria, and thus lots of LPS floating around, your body it automatically going to be pushed in the Th2 direction, making it hard to fight of viral infections, especially in the gut.

High cortisol is another factor that pushes towards Th2. Heavy metal poisoning pushes to Th2.

A high sympathetic and low parasympathetic nervous system activation is though to induce Th2, so such autonomic nervous system dysfunction might be behind Th2 dominance in CFS patients. Dysautonomia itself may have many causes.

Low-intensity exercises like walking, tai chi, and restorative yoga push towards the TH1 response, while higher-intensity workouts and longer durations push the TH2 side of the equation.
 

Valentijn

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Low-intensity exercises like walking, tai chi, and restorative yoga push towards the TH1 response, while higher-intensity workouts and longer durations push the TH2 side of the equation.
How exactly do you propose people with ME do low-intensity exercise, when even that is enough to make us very sick?
 

Hip

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How exactly do you propose people with ME do low-intensity exercise, when even that is enough to make us very sick?
It is useful info for people like me that get PEM from mental exertion, but less so from physical exertion. There are a fair number of PWCs like that. For this subgroup, low-intensity exercise like gentle yoga might be beneficial.

Also, through understanding why, in healthy people, low-intensity exercise pushes towards the TH1 response, while higher-intensity workouts and longer durations push to TH2, may possibly throw light on the mechanics of CFS, and its imbalanced Th1 / Th2 pendulum.
 
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Depending on the subset one belongs to everybody should make their own decisions and report their experiences - we can only learn from each other. I am a strong believer in at least moderate physical exercise and kept on pushing - granted way too much and into a crash. However now I do not suffer from delayed PEM/PENE anymore, instead my body starts pushing back immediately (with inflammatory pain) when crossing the time threshold in aerobic exercise but recovery is within the same day. While this still bothers me, I prefer this response since it gives me more control and better ability to grade my exercise. I don't k now what exactly caused that shift but I do think it is related to changes/improvements in the immune system/gut balance and treatments/therapies. I still do not feel 'normal' or like a healthy control (still have some FM & nerve pain), but somewhere down in the depths of the immune system and its delicate (Th1/Th2) balance lies the answer for us, this is just my gut feeling ;)
 

Hip

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One thing that could well play a role in many cases of CFS is leakage of the LPS endotoxin from the gut. LPS forces the immune system over to Th2.

People with CFS would do well to experiment with taking a leaky gut fixing regimen, like this one:

Leaky Gut Protocol
Saccharomyces boulardii
Grape seed extract 400 mg
Zinc carnosine 1 capsule
Vitamin E 400 iu
N-acetylglucosamine 500 mg
Glutamine 1 heaped tsp
Slippery elm bark 800 mg
Zinc 20 mg
Evening primrose oil 5 ml

This may stop the leakage of LPS, and so may help shift away from Th2.

I found that this leaky gut regimen increased my energy levels just after a few days.
 

Ninan

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B12-"tolerance"?

Hi Rich,

I'm thinking about trying the simplified protocol but I have a question. I've been on B12 for a few years now, with a fantastic, yet diminishing, effect. Started with pills, went on to the common shots and then to methyl-B12. The problem is that the effect has been diminishing all the time. I'm now up in huge doses, 4 ml/day, and the effect doesn'tlast for long. I have to put it out for weeks before it works again, about every other month.

My question: do you know why this happens? And, does this mean that the protocol will have no or little effect on me?

Thanks,
Nina
 
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Hi All, (Uber Pain)
Just found this thread and will follow it. My two cents since being ill for 9 years, XMRV +, Nagalase levels was 1.90...did all testing for chronic infections EBV,CMV, C. Pnuemoniae and many more Low D etc I am TH-2 Dominant Th1 Dormant. I had 65 allergies as a child and received immunetherapy for 9 years to control severe asthma. I fist got illl at 3 months with chicken pox, severe asthma and the mumps. Long story short I think I was always Th-2 weighted. As I out grew my asthma (the tubes in my lung simply got bigger) I became healthier through my teen years and then came down with ME CFS at about 52. Does this scenario fit with anybody here? If so let me know. I believe I have had this thing my whole life and it re-surfaced at 52. Just speculation. With brain fog it's hard to absorb all the posts, but I get it. My first sympom at 52 was pain in the neck, incapaciating pain. Vioxx worked for two years and gave me an ulcer. That's when I got re-sick. I went off all pain meds last December and am suffering. Hope to start GcMAf soon. After three months on LDN the pain is back!