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My Hypothesis on Th2 to Th1 Immunomodulators in CFS

awkwardlymodern

Forcing the past to blend with the future
Messages
52
Has anyone else here tested Th1 dominant? I am definitely Th1 dominant and lack an adequate response to extracellular pathogens, particularly streptococcus. Interestingly, my c4a was normal but my c3a was extremely elevated--my theory is that my immune system is not responding adequately to bacteria, leaving me vulnerable to the effects of bacterial toxins. My case would suggest that Th1 dominance is not a universal protection against ME/CFS, because I definitely have ME/CFS despite my Th1 dominance.

It is interesting, however, that you suggest people shift their immune response to Th1, and then eradicate bacteria with antibiotics. I am already Th1 dominant, and my treatment protocol now is exactly what you would suggest--I'm trying to get rid of my Streptococcus overgrowth with antibiotics.
 

jepps

Senior Member
Messages
519
Location
Austria

@Hip thank you for all the good info. The study posted in the link, suggested, that acupuncture increases Th2. Here is a study and here which describes, that acupuncture balances Th1 and Th2.

A few of the suggested supplements include saccharomyces boulardii, inhibit growths of candida+aspergillus, as well as their biofilms. Only a thought: but as candida releases heavy metals, when addressed, and as mercury switches Th1 against Th2, maybe excreting candida with supplements helps switching Th2 against Th1.
 
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heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
Th1/th2 is said to have limitations as its an old research theory from 1986 on mouse t-helper cells, from what I have read. Quick Google mentions human cytokines rarely fall into exclusive pro th1 or th2 patterns.

I think we need to take this into account. Its possible that something maybe classed as a th2 shifter but have antiviral properties. Its just not black and white with lots of grey areas in the theory.
 

Sidereal

Senior Member
Messages
4,856
Has anyone else here tested Th1 dominant? I am definitely Th1 dominant and lack an adequate response to extracellular pathogens, particularly streptococcus. Interestingly, my c4a was normal but my c3a was extremely elevated--my theory is that my immune system is not responding adequately to bacteria, leaving me vulnerable to the effects of bacterial toxins. My case would suggest that Th1 dominance is not a universal protection against ME/CFS, because I definitely have ME/CFS despite my Th1 dominance.

It is interesting, however, that you suggest people shift their immune response to Th1, and then eradicate bacteria with antibiotics. I am already Th1 dominant, and my treatment protocol now is exactly what you would suggest--I'm trying to get rid of my Streptococcus overgrowth with antibiotics.

For the first 10 years of my illness or more, I was what you might call Th1 dominant with prominent flu-like symptoms, almost constant strep and other infections, daily low-grade fevers in early afternoons etc. Then something changed and the subsequent decade has been characterised by what some might refer to as Th2 dominance with allergies and autoantibodies plaguing me, subnormal body temp, inability to mount a fever etc. I virtually never get normal infections these days, just this bizarre ME/CFS crap we're all intimately familiar with. I would argue this is still the same illness, it's just shifted in expression over time.
 

Hip

Senior Member
Messages
17,824
Th1/th2 is said to have limitations as its an old research theory from 1986 on mouse t-helper cells, from what I have read. Quick Google mentions human cytokines rarely fall into exclusive pro th1 or th2 patterns.

I think we need to take this into account. Its possible that something maybe classed as a th2 shifter but have antiviral properties. Its just not black and white with lots of grey areas in the theory.

That's true. Although it's interesting that in Dr Chia's research with the immunomodulator oxymatrine, he found that when ME/CFS patients responded to oxymatrine (and developed a fever after which much of the enterovirus infection was cleared from their bodies), they all showed a distinct and measurable shift into the Th1 mode (as shown by their cytokine profiles, specifically the IL-12 / IL-10 ratio).

Whereas those patients who did not respond to oxymatrine showed no such Th1 shift in their cytokine profiles.

So a distinct shift to Th1 is associated with getting better from ME/CFS, as a result of taking oxymatrine.


Thus this oxymatrine research suggests that there is something to the Th1 / Th2 theory when it comes to getting better from ME/CFS.


As for these non-responders to oxymatrine, who did not shift into Th1, I keep wondering whether something in their bodies might be blocking or counteracting their ability to move into Th1.
 
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Biarritz13

Senior Member
Messages
699
Location
France
@Hip, I don't know if you're still "involved" in the Th2 to Th1 modulation but here is an interesting study on mice in case you haven't saw it.


Experimental Evidence for Immunomodulatory Effects of Opioids

"The administration of the opioid antagonist naloxone profoundly affected the splenocyte production of the Th1 cytokines IFN-γ and IL-2 and of the Th2 cytokine IL-4 in different strains of mice immunized with the protein antigen keyhole limpet hemocyanin (KLH).74 In fact, acute as well chronic naloxone treatment decreased IL-4 production. On the contrary, IL-2 and IFN-γ levels were increased after naloxone administration. The administration of naloxone seems therefore to stimulate Th1 cytokines while decreasing Th2 cytokines. Given the fact that naloxone is an almost pure antagonist at the μ-opioid receptor, devoid of any intrinsic activity, the effects of the drug are likely to be due to the removal of a regulatory tone exerted by endogenous opioid peptides (Fig. 1).75"


The opioid antagonist naloxone induces a shift from type 2 to type 1 cytokine pattern in normal and skin-grafted mice.


"Opioid peptides affect different immune functions. We present evidence that these effects could be mediated by the modulation of Th1/Th2 cytokine production. The acute and chronic treatment with the opioid receptor antagonist naloxone decreased the production of IL-4 by splenocytes of C57BL/6 and Balb/cJ mice, that present a Th1/Th2 dominance, respectively, immunized with the protein antigen KLH. In contrast, IL-2 and IFN-gamma levels were increased after naloxone treatment. These results indicate that naloxone increases Th1 and decreases Th2 cytokine production. Moreover in C57BL/6 mice, naloxone treatment was able to accelerate skin-graft rejection, a Th1-mediated phenomenon, by increasing Th1 cytokine production. The effect of naloxone could be ascribed to the removal of the regulatory effects exerted by endogenous opioid peptides, which could activate Th2 and suppress Th1 cytokines."


 

Hip

Senior Member
Messages
17,824
@Theodore
Thanks for those papers.

If blocking opioid receptors increases Th1, then that falls in line with the idea that low-dose naltrexone increases Th2.

(Low-dose naltrexone works by blocking the opioid receptors for a few hours, which is thought to then up-regulate endorphins as a compensatory response; so the net result of LDN is increased stimulation of the opioid receptors).
 

Biarritz13

Senior Member
Messages
699
Location
France
When patients improve on oxymatrine, there is a Th1/Th2 change: see this post.

Thank you.

According to you, you didn't improve because you simply didn't tolerate the product or because the problem wasn't in a low Th1/high Th2? Have you had it checked by the way?
 

Hip

Senior Member
Messages
17,824
According to you, you didn't improve because you simply didn't tolerate the product or because the problem wasn't in a low Th1/high Th2? Have you had it checked by the way?

Originally it was a problem of tolerance: I found oxymatrine and other immunomodulators caused significant depression. Some years later, when my health had improved, I was able to tolerate, but got no benefits. I don't know my cytokine profile, as I live in the UK, and the health services here don't check such things in ME/CFS patients.
 

Biarritz13

Senior Member
Messages
699
Location
France
Originally it was problem of tolerance: if found oxymatrine and other immunomodulators caused significant depression. Some years later when my health ahd improved I was able to tolerate, but got no benefits. I don't know my cytokine profile, as I live in the UK, and the health services here don't check such things in ME/CFS patients.

Oh I see...It would be so useful for you as you like to test new things...
 

renski

Senior Member
Messages
338
Location
Honolulu
I'm pretty sure I am Th1 dominate. Explains a lot of things really..

Metagenics ultra inflamx plus 360 seems to be formulated for Th1 dominance..
 
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xrayspex

Senior Member
Messages
1,111
Location
u.s.a.
Yes, I am pretty sure that the depression is caused by the fact that: the antiviral Th1 response increases interferon gamma (IFN-γ), and IFN-γ then causes an increase in the enzyme indoleamine-2-3-dioxygenase (IDO) in the brain, and IDO breaks down tryptophan, and tryptophan is needed to make serotonin, the happiness neurotransmitter.

In summary:

Th1 Response ➤ Increased IFN-γ ➤ Increased IDO ➤ Reduced Tryptophan ➤ Reduced Serotonin ➤ Depression

(Note however that this study contradicts the above standard explanation of interferon-induced depression, and instead suggests an alternate explanation: that although raised IDO is still responsible for the depression, the mechanism of this depression is via IDO's ability to produce kynurenine and kynurenine metabolites such a quinolinic acid, which is linked to depression. In summary: Th1 Response ➤ Increased IFN-γ ➤ Increased IDO ➤ Increased Kynurenine and its Metabolites such as Quinolinic Acid ➤ Depression)

This type of interferon-induced depression is well-known: this very miserable depression occurs in many hepatitis C patients taking intravenous interferon as a treatment for the hep C virus. Also, Dr John Chia, in his study employing intravenous interferon for ME/CFS patients, found that although interferon was very effective, and was able to place many ME/CFS patients he treated into almost full remission for around 2 to 14 months (which is a spectacular result), he found that many of his patients suffered very significant depression during the treatment period. This problem with interferon-induced depression was one of the reasons I believe Dr Chia has largely stopped using intravenous interferon treatment for ME/CFS (that and the very high cost of intravenous interferon, which is in the order of $15,000 for a course of treatment).


I did try taking IDO inhibitors at the same time as taking my Th1 boosting cocktail, in the hope of preventing this depression from occurring, but this did not seem to help. Perhaps these IDO inhibitors were not potent enough, or perhaps I should have used much higher doses of these IDO inhibitors. (Or perhaps I should have heeded the alternate explanation of how IDO causes depression, and taken quinolinic acid inhibitors instead).



The antidepressant drugs paroxetine and low dose amisulpride have been shown to mitigate interferon-induced depression, so it is worth trying these drugs to combat the depression when you take a Th1 boosting cocktail.

But note that not everybody experiences depression from raised interferon levels, so many ME/CFS patients may be able to take the above Th1 boosting cocktail without getting any depression side effects, and thus may potentially experience an improvement in their ME/CFS symptoms from this antiviral Th1 boosting approach.

Apart from my depression (which I suffer from anyway), I did not get any other side effects from this Th1 boosting cocktail.

I am not sure why the various ME/CFS doctors, such as Dr Cheney and Dr Klimas, have not tried a Th1 boosting cocktail like the one I provided above. These doctors note that ME/CFS patients are stuck in the Th2 mode, and that they need to by shifted into the Th1 mode if they are going clear the viruses likely driving their ME/CFS. So it seems to make sense to try to shift your immune system over to Th1 using several Th1 boosting supplements and drugs, not just one supplement.

ok so I haven't had time or energy to go thru and read this whole thread, but I really like Hip's post above, I think the quinolinic acid theory resonates key for me. I want to figure out a way to harness the sweet spot I can feel with that at a certain point of recovering from a cold where still alittle sick but feel better than usual in some ways. I just posted in "immunological" an observation I have about viruses and colds in myself where there is a point I feel better with viral titers raised a little than I do when they are lower, I wrote the following and someone recommended I search th 1 etc to understand it and I came upon this thread, if anyone discovered how to manipulate the quinolinic acid let me know! here is my post from thread I started:

"Sometimes I notice that my mood and brain functioning seem elevated, improved in certain ways when I am at a certain point of getting or having a cold or other viral outbreak. If I take an antiviral like amantadine or valtrex my brain functioning and mood plummet and from the V I get more neuro pain. I have sjogrens autoimmune diagnosis.

If I could capture that certain point of elevated viral titers and harness it I think I would be a happy camper, certainly not cured during that point but just like how I feel more engaged with life.

any others notice this or any theories on why this might be?"



(I am also very chemically sensitive --doesnt take much to react to a medicine, a lick of benadryl can put me to sleep and cause antihisistamine hangover)
 
Messages
61
@Hip Thank you. Th1-Th2 balance is important. And i think that in the immunity is still a lot of pitfalls.
I spread analysis of the chemokines.
upload_2017-2-26_22-48-34.png

I began to use gamma interferon.

Can you help with a list of inducers of cellular immunity and inhibitors of humoral immunity .

And IDO inhibitors lists ?
 
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Hip

Senior Member
Messages
17,824
Can you help with a list of inducers of cellular immunity and inhibitors of humoral immunity .

See this post for Th1 boosters.

There are very few IDO inhibitors; but you can use COX-2 inhibitor drugs or COX-2 inhibitor supplements to inhibit IDO. Propolis is a potent COX-2 inhibitor supplement.
 
Messages
95
Location
SoCal
@Theodore
Thanks for those papers.

If blocking opioid receptors increases Th1, then that falls in line with the idea that low-dose naltrexone increases Th2.

(Low-dose naltrexone works by blocking the opioid receptors for a few hours, which is thought to then up-regulate endorphins as a compensatory response; so the net result of LDN is increased stimulation of the opioid receptors).

Didn't know LDN promotes Th2, curious why Dr. C would prescribe that.