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Can anyone explain TH1/TH2 shift and possible drugs to alter it?

Seadragon

Senior Member
Messages
788
Location
UK
Hi all,

I've only recently joined this board and whilst I have already had a lot of help and learned a bit more about the latest tests and treatment so far (I dropped out of the ME/CFS community for several years having given up on it all for a while), I still need to learn a lot more so I can provide valid reasons for trying appropriate drugs to the new immunologist I am seeing.

I am especially interested in the TH1/TH2 shift basically because I always feel about 50% better, sometimes more, with a virus.

I don't really understand it though - a brief explanation from someone would be helpful so I can discuss it intelligently with the immunologist.

Also what could one take (drugs wise) that could help address this shift and recreate the improvement I get with a virus?

Thanks and love,

Esperanza x
 

richvank

Senior Member
Messages
2,732
Hi, Esperanza.

I believe that the Th1/Th2 shift is caused by glutathione depletion. I doubt if the immunologist will understand this or accept it. Immune modulating drugs provide only temporary help, and do not address the root cause, in my opinion. To really fix this, you have to raise glutathione, and we have found that the way to do this is to lift the partial methylation cycle block, which is upstream of glutathione synthesis in the sulfur metabolism. That's what the methylation protocols do (discussed in another section of these forums). I would suggest viewing the video or scanning the slides (click on the blue print to get the slides) here:

http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/${weburl}

Best regards,

Rich
 

Seadragon

Senior Member
Messages
788
Location
UK
Hi Rich,

I am in the process of starting Freddd's protocol and it's going quite well - at the beginning I could not tolerate the supplements AT ALL but now after several weeks of introducing the supps very slowly and one at a time, things are improving in that way and I do feel some slight improvement already.

I was wondering about LDN or Immunovir to add to this. I think they help the shift????

Love Esperanza x
 

richvank

Senior Member
Messages
2,732
Hi, Esperanza.

I think they do help. I'm glad you are doing a methylation protocol, too, because I think that will get at the root cause.

Best regards,

Rich
 

Seadragon

Senior Member
Messages
788
Location
UK
Which is better LDN or Immunovir?

I'm not sure how these drugs sould be taken (doses, for how long, pulsed etc) for this purpose (shifting the TH1/TH2 balance)

I read LDN should be started at very low doses and maybe titrated upwards (I do worry about LDN - even though it seems the more likely option to work - as I take sleep meds and have severe sleep onset insomnia - couldn't cope with a worsening of that) and Immunovir (which I thried before a long time ago but not int the way it was supposed to be taken) - isn't it supposed to be taken in high "pulsed" high doses?

Love Esperanza x

PS Still would appreciate an explanation of the TH1/TH2 shift from someone if possible - right now I do not even know what these letters and numbers stand for let alone what it actually means!!!!
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,074
Location
australia (brisbane)
Which is better LDN or Immunovir?

I'm not sure how these drugs sould be taken (doses, for how long, pulsed etc) for this purpose (shifting the TH1/TH2 balance)

I read LDN should be started at very low doses and maybe titrated upwards (I do worry about LDN - even though it seems the more likely option to work - as I take sleep meds and have severe sleep onset insomnia - couldn't cope with a worsening of that) and Immunovir (which I thried before a long time ago but not int the way it was supposed to be taken) - isn't it supposed to be taken in high "pulsed" high doses?

Love Esperanza x

PS Still would appreciate an explanation of the TH1/TH2 shift from someone if possible - right now I do not even know what these letters and numbers stand for let alone what it actually means!!!!

LDN would probably be alot cheaper so maybe better to try first?

cheers!!!
 

hixxy

Senior Member
Messages
1,229
Location
Australia
LDN was a bit of a failure for me. I broke out in all these scabby spots all over my back that still haven't gone away and it made my depression worse.

I suspect my gut needs to be fixed first. Round and round we go.

hixxy
 

richvank

Senior Member
Messages
2,732
Hi, Esperanza.

Sorry, I misunderstood. I thought you were looking for what causes the Th1/Th2 shift, not what it is.

Here's a shot at explaining it. It is a little more complicated now, because of the discovery of other kinds of T cells in the past few years, but this is still basically correct:

The T stands for T lymphocytes. They are a type of white blood cell that is found in the blood and in the lymph system,and they are an important part of the adaptive immune system.

They are called "T" because they mature in the thymus gland.

There are different types of T cells. One category is the Th or helper T cells. They are so-called because they help other cells in the immune system to respond appropriately to threats, such as pathogens and toxins.

T cells start out as naive T cells, and then they get converted to the types that are needed. There are two types of helper T cells, Th1 and Th2. Th1 cells act by activating macrophages so that they can attack bacteria that are inside the macrophages. So Th1 cells are formed when the best approach for defending the body is to activate the macrophages. This is called "cell-mediated" immunity. On the other hand, for bacteria that are extracellular, i.e. not inside macrophages, the better approach is to make antibodies that will attach to the bacteria. This is called "humoral" immunity. Antibodies are made by B lymphocytes, which turn into plasma cells. In order to help them to act, Th2 lymphocytes are needed. So the body normally makes an appropriate mix of these two types, depending on what is needed to defend against the various threats that are present.

O.K., now in ME/CFS, this balance goes out of whack. Instead of having the right amount of each, there is a shift to Th2, and the immune system gets stuck there. This is a problem, because now there is not a good defense against intracellular pathogens, such as Chlamydia, mycoplasma and rickettsia. There is also not a good defense against viruses or fungi, including yeasts. It is not a coincidence that these are the types of infections that are found in ME/CFS. They are there because the immune system is not able to effectively defend against them, because of the shift to Th2.

O.K., I think people agree with this, so far. Perhaps what they don't agree on is what causes the shift. In my hypothesis it is caused primarily by glutathione depletion, and I think there is good biochemical evidence for this, but it is still a hypothesis.

If it is indeed caused by glutathione depletion, then raising glutathione must be the answer, and that's what the methylation treatments do.

I hope this helps.

Best regards,

Rich
 

hixxy

Senior Member
Messages
1,229
Location
Australia
Ok. That means Th1/Th2 shift doesn't explain the presence of bacterial overgrowth/dysbiosis and parasites in the intestine? This seems to be an enormous problem for many of us.

Many of us saw dysbiosis as the instigating factor of our disease.
 

richvank

Senior Member
Messages
2,732
Hi, hixxy.

Here's something that is puzzling. I've recently heard that in the gut, the shift may be in the other direction, i.e. to Th1. I don't understand this yet.

Yes, the gut is big in ME/CFS (pun really not intended!), and I still have a lot to learn about this. Dr. de Meirleir is the leader in this aspect.

Best regards,

Rich
 

hixxy

Senior Member
Messages
1,229
Location
Australia
Hi, hixxy.

Here's something that is puzzling. I've recently heard that in the gut, the shift may be in the other direction, i.e. to Th1. I don't understand this yet.

Yes, the gut is big in ME/CFS (pun really not intended!), and I still have a lot to learn about this. Dr. de Meirleir is the leader in this aspect.

Best regards,

Rich

There's very interesting and obviously confuses things even more in this already confusing disease.

hixxy
 

*GG*

senior member
Messages
6,389
Location
Concord, NH
I was wondering about LDN or Immunovir to add to this. I think they help the shift????

Love Esperanza x

I have been on LDN for about 2.5 years now. I did a lot of changes at the same time, got tired of changing1 thing at a time, and trying to see if things got better etc...

I have been ill 9 years now. I had trouble with LDN at first, although I was in massive pain and had lidocaine infused into my blood stream to help deal with the pain/insomnia. the lidocainse dropped the pain level down 2 to 3 notches, from the max. FYI

I believe I started at 1.5mg and slowly tapered up to 4.5mgs, probably over the course of a month or 2. I don't have the flu like symptoms like I used to have, and got back on my bicycle last year, after taking the previous year off for recuperating. I don't experience the PEM like I used to, although I did a little snowboarding this past winter, and that kicked my but pretty well!

GG

PS PM if you have any questions.
 

richvank

Senior Member
Messages
2,732
Stress will also cause a shift toward Th2.

Hi, adreno.

Yes, that's right. I suspect that prior to onset of ME/CFS, when the person is under a load of stressors of various sorts, cortisol initially rises, and stays high for some time. This suppresses inflammation and also shifts the immune response to Th2. In addition, it contributes to glutathione depletion. Then, ME/CFS onset occurs when glutathione has dropped enough to produce the functional B12 deficiency, which leads to the partial methylation cycle block. Over time with this disorder, the hypothalamus and pituitary go low in glutathione, and that affects the amount and diurnal variation of the ACTH secretion by the pituitary, which in turn lowers cortisol. But by that time, the glutathione depletion in the immune system cells has solidified the Th2 shift, which remains while the person has ME/CFS. So I suggest that the stress starts the shift via elevated cortisol, and then the glutathione depletion takes over and maintains the Th2 shift.

Best regards,

Rich
 

adreno

PR activist
Messages
4,841
Hi Rich,

I don't disagree with you, but there could be other mechanisms involved in the hypocortisolism seen in ME. Desensitization of CRH/ACTH receptors is likely, in my view. And upregulation of GR receptors in the hypothalamus (enhanced feedback inhibition).

Also the drop in neurotransmitters seen, which could be explained by a partial methylation block, but equally with viral infections. Viruses particularly mess with acetylcholine and norepinephrine receptors, both which enhance CRH release.

There could also be adaptive mechanisms at play, lowering cortisol to protect the cells from any further catabolic action, after the prolonged enhanced release of cortisol. Maybe some epigenetic mechanism, I don't know.
 

richvank

Senior Member
Messages
2,732
Hi Rich,

I don't disagree with you, but there could be other mechanisms involved in the hypocortisolism seen in ME. Desensitization of CRH/ACTH receptors is likely, in my view. And upregulation of GR receptors in the hypothalamus (enhanced feedback inhibition).

Also the drop in neurotransmitters seen, which could be explained by a partial methylation block, but equally with viral infections. Viruses particularly mess with acetylcholine and norepinephrine receptors, both which enhance CRH release.

There could also be adaptive mechanisms at play, lowering cortisol to protect the cells from any further catabolic action, after the prolonged enhanced release of cortisol. Maybe some epigenetic mechanism, I don't know.

Adreno,

Good points. Thanks.

Rich
 

Jenny

Senior Member
Messages
1,388
Location
Dorset
Hi, adreno.

Yes, that's right. I suspect that prior to onset of ME/CFS, when the person is under a load of stressors of various sorts, cortisol initially rises, and stays high for some time. This suppresses inflammation and also shifts the immune response to Th2. In addition, it contributes to glutathione depletion. Then, ME/CFS onset occurs when glutathione has dropped enough to produce the functional B12 deficiency, which leads to the partial methylation cycle block. Over time with this disorder, the hypothalamus and pituitary go low in glutathione, and that affects the amount and diurnal variation of the ACTH secretion by the pituitary, which in turn lowers cortisol. But by that time, the glutathione depletion in the immune system cells has solidified the Th2 shift, which remains while the person has ME/CFS. So I suggest that the stress starts the shift via elevated cortisol, and then the glutathione depletion takes over and maintains the Th2 shift.

Best regards,

Rich

Hi Rich

So what do you think is going on with those of us who have high cortisol after many years of illness? (I have this, and first got ill 30 years ago.)

Thanks as always!

Jenny
 

xchocoholic

Senior Member
Messages
2,947
Location
Florida
I don't understand this completely but dr fasano has info on this too. He says it happens in the gut. I can't give you the link but if you google fasano th1 th2 you'll find it. Tc .. X
 

Charles555nc

Senior Member
Messages
572
1. What does RichVank think of the marshal protocol, (benicar for lowering one of the two forms of vitamin D, so the VDR isnt overwhelmed).

2. As far as improving ingestion, I started improving on my "regimen" that Ive posted alot in the general forums and started to continue to improve by doing gallbladder cleanses (theres a common duct for the liver, pancreas and gallbladder fyi), I actually adding a bit to it, and I can clearly see some of the stones are infected afterwards...

3. I saw improvement with 25mg DHEA, but the added hormones affected my skin and Rosacea, so Im switching to 7 keto DHea, which should not break down to testosterone and estrogen. Dhea in general is supposed to boost immunity.... do you have a position on low dose immune boosting hormone supplementation, Rich?


____________________
Revised Gallbladder flush:

-(take no supplements or apple containing product not mentitioned after the first 5 days (days 6 and 7))

-take malic acid 800mg twice a day for first 5 days. This helps to dissolve gallstones a bit so they are able to leave the gallbladder.

-on the 6th day, eat no fat the whole day and no eating at all after 12pm, at 2:30pm take 2 teaspoons of epsom salts, 3:00 1 teaspoon epsom salt, 3:30 take another teaspoon, 4:00pm take the fourth and final teaspoon of epsom salt. With every dose of epsom salt I recemmend taking 2 grams sodium ascorbate (vit c) to prevent feeling sick and extra salt. Epsom Salt dialates the common duct, allowing larger stones and debris to pass into the intestine.

4:00pm-8:00pm Drink plenty of pure water.

-at 8:30pm take a half cup of extra virgin olive oil and half cup lemon or grapefruit juice, (if you have done at least 15 flushes already then at 8:45pm take another half cup extra virgin olive oil and half cup lemon or grapefruit juice) You may feel sick afterward but try to keep your stomach calm. I drink a full sugar coke (regular coke, small bottle) about 10 minutes after this. The sugar opens up the pancreas to release insulin ( and shares a common duct which is now dialated). Even the pancreas can develop stones.

-get comfortable and rest for an hour. Take 4 grams vitamin c to absorb toxins. Get to sleep when you can. You may feel nauseous.

-on the 7th day's morning, upon waking, take another 10-15 grams sodium ascorbate (vitamin c) to exceed bowel tolerance, causing a bowel movement, and to detox and push out the old bile from the intestines.

Start eating very light for the next 5 or 6 hours. Like a bananna or oatmeal or a salad. After about 2pm you can start eating normally again (dont over do it).

You will pass green stones and debris in your bowel movements. I lost 35 lbs of fat over 4 or 5 flushs this way and Im up to about my 12 cleanse. My skin and energy improved a bit and I am actually did one last night. They can be very tough to do though.
___________


P.S. Glad to see such an active thread!
 

Crux

Senior Member
Messages
1,441
Location
USA
I've read that zinc deficiency is associated with lowered Th1 activity. I've also read that with zinc deficiency, cortisol may increase. ( probably to compensate for the inflammation)