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New Hypothesis on Th2 to Th1 Immunomodulators in CFS

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Hip, Jan 27, 2011.

  1. Hip

    Hip Senior Member

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    Preamble:

    Dr Cheney has observed that immunomodulators such as imunovir, that shift the immune system balance from a Th2 (antibacterial) response to a Th1 (antiviral) response, often get good results in CFS patients initially, but then the gains seem to disappear after some months. Many CFS patients have experienced this themselves.

    Dr Cheney speculates that the reason for this is that the body gets used to immunomodulators: that the body builds up a tolerance to them after some months, thereby explaining why their good effects wear off. Dr Cheney suggests you should take regular breaks from immunomodulators, to prevent this tolerance from manifesting.

    New Hypothesis:

    It occurred to me that there may be an entirely different explanation for why the good effects of Th2 to Th1 immunomodulators disappear after a few months of usage, which is as follows:

    When taking Th2 to Th1 immunomodulators, and the immune system shifts towards the Th1 response, this works well for killing off your viruses; but since at the same time your Th2 is down-regulated, so it is conceivable that the bacteria in your body then start to proliferate more and more, because of the diminished Th2 response. Thus although you initially feel better due to a reduced viral load, you may soon start to feel bad again, because the bacteria are building up in your body.

    From the viewpoint of this alternative explanation, the reason pulsing your Th2 to Th1 immunomodulators (having breaks from taking them) is helpful may be less to do with preventing a tolerance from manifesting, and more about allowing the Th2 immune response to ramp up again for a while, in order to kill off the bacteria that proliferated while you were on the Th1 side.

    However, presumably during these regular breaks from taking immunomodulators, the viruses in your body will unfortunately start multiplying again, while the bacteria are now being killed by the Th2 immune system.

    Indeed, perhaps CFS arises in the first place due to patients having both pathogenic viruses AND bacteria in their bodies, and so that every time the immune system fights of one type of pathogen, the other type then sneakily re-emerge.

    In a sense, people with CFS may be trapped in a long dark alley, with viruses attacking from one end, and bacteria from the other. When you direct your energy to fight off the viruses, the bacteria come to get your from behind, and vice versa. So you never get out of the alley.

    I don't know enough about the function of the immune system to say with any certainty whether the above scenario is in fact possible, but I thought I'd throw it out for general discussion and comments.


    Possible Way out of the Alley

    One possible solution, it would seem, to this dark alley scenario is to take antibiotics at the same time as taking Th2 to Th1 immunomodulators. In this way, you let the Th1 immune system tackle the viruses, and let the antibiotics keep the bacterial populations in your body in check.

    With this approach, you would not need to take any breaks from the immunomodulators; so you maintain an uninterrupted ongoing full-on Th1 assault on the viruses, until they are hopefully pummeled into submission.

    Note that if, on trying this Th2 to Th1 immunomodulators + antibiotics approach, it does seem to work (meaning that gains experienced do not disappear even after several months on continuous immunomodulators), it would indicate that there is something to this idea.

    Ideally, if possible it is best to take the right antibiotics (or antibacterial herbal supplements): ones that best target the specific pathogenic bacteria you have in your body (if you have this information at hand, from an intestinal stool analysis for example).
    Last edited: Nov 21, 2013
  2. Crappy

    Crappy Senior Member

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    I am curious how fresh your information is? Does Dr. Cheney still treat based on Th1-Th2?

    Thanks
  3. ukxmrv

    ukxmrv Senior Member

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    I have taken Imunovir and antibiotics at the same time but not at the start of Imunovir and not for long periods. Several different types of AB's due to sinus and other infections.

    Imunovir helps my viral symptoms (sore throat, glands etc). Originally I pulsed the Imunovir (a la Cheney) and noticed an immediate improvement. Maybe it was the pulsing method but I didn't have a downturn in effect after months.

    Then I had a long break from Imunovir as I could not get it. My health went downhill. Took antibiotics but no improvement (AB's don't usually improve my ME symptoms and I've tried different protocols over years)

    Back on the Imunovir and also some antibiotics. I'll post here again if I notice anything specific or relevant.
  4. Otis

    Otis Señor Mumbler

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    Hi ukxmrvm

    What's your Imunovir dosage/schedule?

    Thanks,
    Otis
  5. ukxmrv

    ukxmrv Senior Member

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    Hi Otis,

    I'm working back up onto an old Cheney protocol that I used to use years ago. He may have something new by now.

    The end result will be (I'm only only 3 a day at the moment at the most)

    Week one, take 5 tablets a day, Monday through Friday, and none on the weekend. Week two, take 2 tablets a day, Monday through Friday, and none on the weekend. Repeat this cycle. But do not treat every month. Do two months on and then one month off of this "pulsing" dose.


    XMRV+
  6. Hip

    Hip Senior Member

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    Not sure what Cheney does on a day to day basis, but the general use of immunomodulators is common in CFS.

    A lot of the drugs/supplements prescribed and used by people with CFS do shift from Th2 to Th1. These Th2 to Th1 immunomodulator drugs/supplements include:

    Imunovir (isoprinosine), inosine, azithromycin, oxymatrine, naltrexone, Epicor (Saccharomyces cerevisiae), astragalus, colostrum, transfer factor, beta sitosterol.

    As far as I know, Th2 to Th1 shifting is still a reasonably popular approach.
    Last edited: Nov 21, 2013
  7. garcia

    garcia Aristocrat Extraordinaire

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    The kind of bacterial co-infections that ME/CFS people have are intracellular bacterial infections such as Chlamydia pnuemoniae, Mycoplasma & Lyme (& lyme coinfections). These all require a Th1 response just like viral infections.
    cigana likes this.
  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    im having quite good success with a russian immune modulator called cycloferon and have a thread on it, i decided to use it as it was alot cheaper to use then imunovir, but i also understand the need to take breaks from the immune modulators. I have thought of alternating between cycloferon and immunovir, maybe swapping every 2 months or so. Doing this would get rid of the need of being off an immune modulator altogether and losing any gains obtained while on cycle. Any thoughts on this type of regime???
  9. Hip

    Hip Senior Member

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    That is true: it is of course more accurate to say that the Th1 response fights intracellular pathogens (and intracellular forms of pathogens), and the Th2 response fights extracellular pathogens. So for the bacteria that are intracellular (or can have intracellular forms) like Chlamydia pnuemoniae and Borrelia, these would appear to require a Th1 response to fight them, as you mention.

    I was thinking more of the extracellular bacteria like Staphylococcus, Streptococcus, Klebsellia, Escherichia Coli - the sort of bacteria that are often found in high populations in a dysbiotic state in the intestines of people with CFS.

    Although even here it is complex, as I think some of these bacteria can have intracellular forms as well as extracellular forms. In fact, I read that there is increasing evidence now for Staphylococcus being able to switch to an intracellular form.

    I fact the hypothesis give above could reformulated: instead of talking about viruses versus bacteria, you might change this to: intracellular pathogen forms (IPFs) versus extracellular pathogen forms (EPFs).

    That is to say, when you shift to Th1, you kill IPFs, but may allow EPFs to increase in number. Then if you swing back to Th2, you do the reverse: you kill EPFs, but may allow IPFs to increase in number.

    So the dark alley way has intracellular pathogen forms at one and, and extracellular pathogen forms at the other.

    Again, let me say that I don't know if there is any merit to this idea, but it's something that might be worth considering.
  10. Hip

    Hip Senior Member

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    It is certainly something worth trying.

    Not sure how increased interferon via cycloferon, and increased Th1 response via Imunovir (or other means) would interact, but I may myself try both together at some point.
  11. knackers323

    knackers323 Senior Member

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    Hi Hip,

    Did you ever try this?

    This is an interesting idea. Maybe cfs is a result of having two type of infections, auto immune response or something that is requiring the immune system to give both a th1 and th2 response (and I heard there may be other arms as well) at the same time.

    Therefore it is fighting a battle on two fronts, doesn't know where to go, runs itself down and isnt actually taking care of either infection.

    Maybe? What you think
    Last edited: Nov 21, 2013
  12. Hip

    Hip Senior Member

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    @knackers323
    What I did try was a cocktail of supplements that promote the Th1 response. My idea was that if you strongly shift your immune system into the Th1 mode, you are going to give the viruses in your body a really good fight.

    The Th1 Boosting Cocktail I devised comprised:
    Reishi, astragalus, beta sitosterol, low dose naltrexone, inosine, IP6 (inositol hexaphosphate), beta glucans, glutathione, glutamine, colostrum, chlorella, silica, vitamin E, zinc, transfer factor, and cetirizine (an antihistamine).

    All of the above supplements and drugs each individually act to shift the immune system into the Th1 mode (and reishi and astragalus also boost interferon alpha).

    People with ME/CFS often just take one Th1 inducer, such as inosine or oxymatrine; but I thought: why stop at just one? Why not take a dozen or so Th1 inducers together, in a cocktail!

    Good idea I thought, but I ran into a problem: in the past I found that some Th1 inducing supplements can make me depressed when I take them; and unfortunately, when I took the above cocktail of around a dozen or so Th1 inducers, I quickly became very depressed, so I had to stop taking the cocktail.

    However, for anyone who does not get this depression side effect from Th1 inducers, this cocktail approach to shifting into the Th1 mode may well be worth trying.

    If I could find a way to prevent the depression side effect, I would definitely try taking this Th1 cocktail for a few months. I don't think anyone has ever tried such a super-power Th1 inducing cocktail for ME/CFS, for the purpose of trying to wipe out the viral infections.
    Last edited: Nov 21, 2013
    cigana likes this.
  13. knackers323

    knackers323 Senior Member

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    Interesting. Do you know why raising the th1 response causes depression?

    If you were to take something to dampen the th1 response it could lessen or eliminate symptoms but cause the infection to spread.

    Is this correct?
  14. Hip

    Hip Senior Member

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    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.
    Last edited: Dec 16, 2013
  15. lansbergen

    lansbergen Senior Member

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    My immune modulator increases interferon gamma production but does not give me depression
  16. Hip

    Hip Senior Member

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    And many ME/CFS will be like you: they will not suffer from depression as their interferon gamma levels are ramped up. This depression only occurs in a substantial subset, but not all, patients. If you are one of the lucky ones that do not experience depression from interferon, you might consider the Th1 Boosting Cocktail (if you are the adventurous, experimental type).

    Which immunomodulator are your taking, by the way?
  17. lansbergen

    lansbergen Senior Member

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    levamisole
  18. Ema

    Ema Senior Member

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    I've taken everything on this list at one time or another and am currently still taking most of it. I'm no longer taking chlorella or my mushroom mix. I'm also taking a break from LDN but was thinking of starting it back up again.
  19. mermaid

    mermaid Senior Member

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    About a year ago I had the same idea, though I didn't take as many TH1 shift supplements/drugs as you were taking. I took astragalus, LDN, betaglucans, plus one other I researched but can't remember what it was now.

    I definitely shifted something at the time as the nature of my viruses changed and were not so unpleasant. (I used to feel as if I was fighting the virus for days but nothing would come of it.) Unfortunately though I seemed to get more rather than less for a while during this treatment. I had a better summer this year, but now I am getting sore throats back again, though not such bad symptoms as I used to get, on the whole.

    I did not get depression though as I found that LDN was the best antidepressant around. I stopped taking it as it did nothing for my immune system that I was aware of, but if I ever had a bad bout of depression I think I would choose it over any other antidepressant!
  20. knackers323

    knackers323 Senior Member

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    So just to clarify.

    If we have an increases immune response due to an infection we can't get rid of and then we try to divert the immune system away from fighting it with immune modulators.

    This is not counter productive?

    Is this true if we are taking something to kill the infection or not?

    Or should we only try to divert the immune response when it is an auto immune response that we can't find a reason for? Thanks
    maryb likes this.

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