My Hypothesis on Th2 to Th1 Immunomodulators in CFS

[Dufresne]

It was at his 2009, Fairfax lecture where he wheeled out the redox thing. He has to be absolutely right about this. I'm surprised no one focused on it earlier: without adequate cellular energy you end up vulnerable to intracellular infection and this further drives you toward humoral dominance. I used to have the lecture on DVD but seem to have misplaced it. Here's a recap though:

http://forums.prohealth.com/forums/...-cheney-talk-fairfax-va-april-25-2009.203809/

Cheney's most recent talk:

Dr Klinghardt has been sending people in for HLA DR testing that he diagnoses as having "Lyme Disease". Various other LLMD's are doing the same. This seems to have caught on in the Lyme world but not yet the ME/CFS world. We should really start a poll here on PR to get a rough idea of the percentage of people with ME that are testing positive for these genes. I wish I had the link to the doctors' blogs that reported the high percentage but I don't have that now. Sorry. @slayadragon linked to one such blog somewhere on the forum here.

 

[Dufresne]

@Dufresne
Certainly the innate immune system is also involved in ME/CFS. The complement system is of course the major part of the innate immune system, and in ME/CFS patients it has, as you say, been shown that C4a in the complement system is activated after exercise, but not in healthy controls. It has also been shown that C4a is activated in chronic Lyme disease.

There are three basic pathways within the complement system: the classical pathway, the alternate pathway, and the lectin pathway. In ME/CFS, you have C4a activation within the lectin pathway, as a result of exercise.

It certainly might be a good idea to try to inhibit the lectin pathway in ME/CFS. Some time ago I was actually looking for drugs or supplements that can inhibit the complement system, and there are a few of them, including olive leaf extract, boswellic acids (from frankincense), rosmarinic acid (from rosemary and lemon balm essential oils), bladderwrack herb and Ephedra. However, these all inhibit the classical pathway and the alternate pathway, but unfortunately not the lectin pathway. I could not find any medication that inhibits the lectin pathway.

The lectin pathway of the complement system is activated when mannose-binding lectin or ficolin attaches to certain sugars found on the surface of pathogens.



But going back to the Th1 / Th2 balance: the important thing to note about the Th1 / Th2 balance is that the activation of one automatically creates an inhibition of the other. So this means that in ME/CFS, where is Th2 is over-activated, this automatically means that Th1 will be simultaneously inhibited, and since Th1 is responsible for fighting viruses, this is not good news.

I think the best way to control the leptin pathway would be a low carb/sugar diet. This is what Shoemaker recommends. Also he prescribes Actos for calming the inflammation as well as fish oil.

If the TH1-TH2 is a zero sum game then the fact that we're redox shifted due to low cellular energy, and necessarily TH1 compromised, could be a massive contributor to this problem. No?

 

[slayadragon]

http://www.drdaveou.com/blog/?p=406

 

[Hip]

I think the best way to control the leptin pathway would be a low carb/sugar diet. This is what Shoemaker recommends. Also he prescribes Actos for calming the inflammation as well as fish oil.

If the TH1-TH2 is a zero sum game then the fact that we're redox shifted due to low cellular energy, and necessarily TH1 compromised, could be a massive contributor to this problem. No?

According to this study, a diet high in sugars, especially fructose, is needed to inhibit the lectin pathway of the complement system. This of course is assuming that we want to inhibit the lectin pathway.

Can you explain what you mean by the term "redox shifted."

I don't think we should simply be looking at this as Th1/Th2 being a zero sum game. ME/CFS specialists believe it is important to bring the balance of Th1/Th2 back to normal, because ME/CFS patients are shifted too far towards Th2. I suggest this means not only taking drugs or supplements that boost Th1, but also addressing issues that sabotage the desired shift to Th1, such as the factors listed above in this thread — factors like LPS toxin from bacteria, that mire you in Th2. I suggest you'd want to remove as many factors as you can that mire you in Th2, so that you stand the best chance to move towards the desired Th1.

Once you are shifted back towards Th1, your body will start fighting the viruses more fiercely.

 

[Hip]

In terms of redox, lack of intracellular glutathione will shift you towards the undesired Th2 (ref: 1), so taking supplements like whey protein isolate, which boosts intracellular glutathione, is a good idea.

 

[Dufresne]

Unfortunately, the immune system is not very good at working in both Th1 and Th2 at the same time. So if the immune system is working hard in Th2, then is will only be working quite weakly in Th1, and vice versa.

This leads to the concept of the Th1 / Th2 balance of your immune system: that is, you immune system is a bit like a pendulum that can swing between Th1 and Th2. When your immune system is working hard in Th1 mode, then Th2 will be weak, and when your immune system is working hard in Th2 mode, then Th1 will be weak.

Aren't you saying here that it's basically a zero sum game?

Cheney explains 'redox shifted' as that state where you're dealing with oxidative stress and low cellular energy, and that you can't fight off intracellular infections. There's an optimal place to be and everyone with ME/CFS is outside this. Would this not necessitate a shift toward humoral dominance?

Shoemaker suggests a complex carb-free diet to lower lectin. The sugar-free thing is mine and I use this for other reasons. Thanks for the correction.

 

[lansbergen]

Cheney explains 'redox shifted' as that state where you're dealing with oxidative stress and low cellular energy, and that you can't fight off intracellular infections. There's an optimal place to be and everyone with ME/CFS is outside this. Would this not necessitate a shift toward humoral dominance?.

Humoral dominance when there is no or low seroconversion after vaccination?

 

[Hip]

Aren't you saying here that it's basically a zero sum game?

Cheney explains 'redox shifted' as that state where you're dealing with oxidative stress and low cellular energy, and that you can't fight off intracellular infections. There's an optimal place to be and everyone with ME/CFS is outside this. Would this not necessitate a shift toward humoral dominance?

Shoemaker suggests a complex carb-free diet to lower lectin. The sugar-free thing is mine and I use this for other reasons. Thanks for the correction.

It is a zero sum game, but that is not to say that there is nothing we can do.

It is a zero sum game because when some factor (such as a bacterial gut infection) in your body triggers an increase in the Th2 response, this unfortunately means you get a simultaneous reduction in the Th1 response. So it is important to look at the factors in your body that are triggering a Th2 response, and try to eliminate those factors, so that the immune system is able to work within the Th1 response — the response that fights intracellular infections such as viruses and intracellular bacteria that are thought to drive ME/CFS.

Hence taking antibiotics to reduce any gut infections should help lower Th2, and this in turn will help ramp up Th1.

Regarding this "redox shift" that Dr Cheney talks about: does he explain the mechanism by which this lowers Th1, and thus prevents the immune system fighting off intracellular infections? The only connection I am aware of between the redox state and the immune system is the one mentioned above: that low intracellular glutathione (glutathione being the most important antioxidant within cells) will cause a shift away from Th1 and towards Th2.

But I would be very interested to learn of any other mechanism by which oxidative stress can inhibit the Th1 response.

I am not sure that there is a "humoral dominance" in the same way that there is a "Th2 dominance" or "Th1 dominance", because unlike the Th1 and Th2 immune responses which as explained are in competition with each other (with the dominance of one then suppressing the other), I don't believe an active humoral response suppresses any other parts of the immune system.


Regarding Shoemaker's suggestion of a complex carb-free diet to lower lectin: I believe this refers to lowering dietary lectins (dietary lectins such as wheat agglutinin), rather than reducing the lectin pathway of the complement system. I am not aware of any link between the two. Dietary lectins are bad because they can damage the intestinal lining in sensitive people. I actually follow a low lectin diet myself, just as a precaution. The most problematic dietary lectins that you want to avoid are those found in grains, beans, and in the nightshade family of foods.

 

[Hip]

To give some context to the ideas expressed in this thread:

If you look at Dr John Chia's research using the herbal immunomodulator oxymatrine (oxymatrine acts as a Th2 to Th1 shifter), Chia found that 25% of his ME/CFS patients responded well to oxymatrine, and got significant improvements in their symptoms. Along with these improvements, his patients showed a shift in their immune systems from Th2 to Th1, suggesting that these improvements in symptoms arose due to the body now fighting off the intracellular viral infections.

However, what about the other 75% of patients who did not really respond to oxymatrine? Why did the immune systems of this 75% not shift towards Th1, and fight off the intracellular viral infections?

I think the answer may be because these non-responders to oxymatrine may have had several factors in their bodies blocking the Th1 response. These Th1 blocking factors are the ones discussed in this thread: they are the factors which promote a Th2 response in the body, thereby blocking the desired Th1 response.

So my idea is that if you were to remove these Th2-promoting factors that block Th1, you may then become a responder to oxymatrine (or to other Th1 boosting immunomodulators like inosine).

In other words, by removing these Th1 blocking factors, all ME/CFS patients (not just 25%) may then response favorably to oxymatrine or other immunomodulators, and so get substantial improvements in their ME/CFS.


A transcript of a presentation given by Dr John Chia detailing his work with oxymatrine treatments for ME/CFS is to be found >> HERE.

 

[Dufresne]

Humoral dominance when there is no or low seroconversion after vaccination?

I believe seroconversion is an aspect of adaptive immunity, not innate immunity. Also I didn't know this was low in ME/CFS patients.

Concerning the TH1-TH2 thing, I think the mechanism by which we sensitize to chemicals and other substances remains unknown. I can sensitize to water. But if I take that same water and put a tea bag in it I'm fine so long as I use a different tea everyday in my four day rotation. Our sensitization starts as vibrational, as vague and new agey as that sounds, but it should be considered a part of adaptive immunity. If our system then goes on to develop antibodies to the substance this then becomes measurable as a TH2 reaction. However this is not going to happen with everything. So is a sensitivity to a chemical a TH2 reaction? No. So how do we classify it?

 

[lansbergen]

I believe seroconversion is an aspect of adaptive immunity, not innate immunity. .

Thats right

So is a sensitivity to a chemical a TH2 reaction? No. So how do we classify it?

I do not have it so I have not given it much thought. I focus on the infection I suspect.

The innate immune response is not specific. It can react to anything it does not trust.

I thought it only serves to overcome the time till the adaptive immune response kicks in. When the adaptive immune system fails to do that the innate response has to carry on.

 

[Dufresne]

I do not have it so I have not given it much thought. I focus on the infection I suspect.

The innate immune response is not specific. It can react to anything it does not trust.

I thought it only serves to overcome the time till the adaptive immune response kicks in. When the adaptive immune system fails to do that the innate response has to carry on.

Innate immunity is ancient and completely inherited. It's the same for all of us and only reacts to certain things. Mold and bacterial fragments called LPS are some of these.

My point with the chemical sensitivities is that we think of it as part of the TH2 dominance in our condition. It is not a TH2 reaction, that's why it's controversial. It really shouldn't be, as they can show inflammation as a result of exposures. There are studies to suggest this is only the case when sufferers can actually smell it. Personally I don't buy that. They did the same thing with EMF studies, claiming supposed sufferers could not tell the difference in a blinded study. These studies are, in my opinion, politically motivated. But I digress, my point with the chemical sensitivity is that if it's not part of a TH2 reaction, don't we need a more accurate term to describe our situation?

 

[lansbergen]

Innate immunity is ancient and completely inherited. It's the same for all of us

If it was the same in everybody there could be no difference in outcome.

 

[Dufresne]

If it was the same in everybody there could be no difference in outcome.

The things we react to with innate immunity are the same. Some of us do it more effectively than others, as Shoemaker describes.

 

[lansbergen]

The things we react to with innate immunity are the same. Some of us do it more effectively than others, as Shoemaker describes.

No diversity, no mutations? It all stayed the same in every living being from the beginning of innate immunity evolution? I doubt that very much.

 

[Dufresne]

I had live blood analysis done twice a couple years ago. This is done under a dark field microscope while the patient is fasting. The first time the blood looked as expected. The second time I had taken wormwood with my morning meal to be as clear headed as possible for the appointment. An interesting thing happened. I had fasted for the recommended amount of time but the naturopath said my blood looked as if I'd just eaten a half hour before the appointment. He could actually see particles from my meal in the blood. I think it's possible that the wormwood decreased my TH2 immunity to the point that it wasn't clearing these. This might indicate that it really is a great shifter as Cheney says.

 

[JBB]

To give some context to the ideas expressed in this thread:

If you look at Dr John Chia's research using the herbal immunomodulator oxymatrine (oxymatrine acts as a Th2 to Th1 shifter), Chia found that 25% of his ME/CFS patients responded well to oxymatrine, and got significant improvements in their symptoms. Along with these improvements, his patients showed a shift in their immune systems from Th2 to Th1, suggesting that these improvements in symptoms arose due to the body now fighting off the intracellular viral infections.

However, what about the other 75% of patients who did not really respond to oxymatrine? Why did the immune systems of this 75% not shift towards Th1, and fight off the intracellular viral infections?

I think the answer may be because these non-responders to oxymatrine may have had several factors in their bodies blocking the Th1 response. These Th1 blocking factors are the ones discussed in this thread: they are the factors which promote a Th2 response in the body, thereby blocking the desired Th1 response.

So my idea is that if you were to remove these Th2-promoting factors that block Th1, you may then become a responder to oxymatrine (or to other Th1 boosting immunomodulators like inosine).

In other words, by removing these Th1 blocking factors, all ME/CFS patients (not just 25%) may then response favorably to oxymatrine or other immunomodulators, and so get substantial improvements in their ME/CFS.

I'm sure 52% respond to oxymatrine / equilibrant according to a video with Dr Chia??

I don't seem to be one of them...yet...have been on oxy for 1 month at full dose and now moving up to 9 tablets (self dosing) as no effect. His son took 9 per day. Need to trial for at least 3 months though.

I think that's an interesting idea and I would love to hear if anyone has tried this? I imagine the problem is that there are so many things which can shift the immune system finding the thing / combination of things would be very difficult. Viruses aren't easy to get rid of as a start.

Have you got any suggestions about what seems to be the most important areas Hip?

Very interesting ideas.


Best wishes,

J

 

[consuegra]

JBB, let me give you a good starting point. Try looking for mycotoxins through the Real Time Labs test. 93% of Brewer's patients tested positive for one of three measurable mycotoxins. Brewer is attempting to treat these patients at this moment with several things including nebuized colloidal silver.

The idea that something is standing in the way of Dr.Chia's patients, keeping them from responding to oxymatrine is fascinating. This concept could be applied to many non-responders. It makes sense, that something else is in the way.
Mycotoxins are an obvious one. I suggested this to Dr.Chia.

Your can read the post on Dr. Joseph Brewer on cfspatientadvocate.blogspot.com

http://cfspatientadvocate.blogspot.com/2013/04/dr-joseph-brewer-and-mycotoxins.html

This entire thread is very interesting.

Chris

 

[JBB]

JBB, let me give you a good starting point. Try looking for mycotoxins through the Real Time Labs test. 93% of Brewer's patients tested positive for one of three measurable mycotoxins. Brewer is attempting to treat these patients at this moment with several things including nebuized colloidal silver.

The idea that something is standing in the way of Dr.Chia's patients, keeping them from responding to oxymatrine is fascinating. This concept could be applied to many non-responders. It makes sense, that something else is in the way.
Mycotoxins are an obvious one. I suggested this to Dr.Chia.

Your can read the post on Dr. Joseph Brewer on cfspatientadvocate.blogspot.com

http://cfspatientadvocate.blogspot.com/2013/04/dr-joseph-brewer-and-mycotoxins.html

This entire thread is very interesting.

Chris

Thanks @consuegra. Very interesting indeed.

So as I understand it from wiki:

"A mycotoxin (from Greek μύκης (mykes, mukos) "fungus" and τοξικόν (toxikon) "poison")[1][2] is a toxic secondary metabolite produced by organisms of the fungi kingdom, commonly known as molds.[3]"

...and according to Brewer about 90% of us have these. So is the conclusion from this that 90% of us have toxic mold poisoning?

I've done FIR saunas nearly every day for about a year with no effect what soever. I wonder if I have detoxed these mycotoxins??

What did Dr Chia have to say when you suggested this to him? Very interested to hear what he thought!


Best wishes,

J

 

[consuegra]

JBB,

Brewer thinks that these mycotoxins take up residence in the sinuses. He thinks, in questioning patients, that the exposure could be as long ago as 25 years. While FIR saunas apparently work on some items, these colonized mycotoxins are not one of them. Brewer believes that you need to go after them directly and try to dislodged them or knock them out of the sinuses. At some point we might see his results of treatment modalities.

I only suggested to Dr. Chia that certain items might stand in the way of Oxymatrine working in some people and perhaps that could be mycotoxins (among a bunch of things). While Chia did not have a specific response, I know him as a clinician who is not afraid of following up on ideas that have some potential.

Chris
cfspatientadvocate.blogspot.com