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Downturn in IL-17 levels linked to gut barrier breakdown

Discussion in 'Other Health News and Research' started by natasa778, Sep 14, 2013.

  1. natasa778

    natasa778 Senior Member

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    http://www.jimmunol.org/content/186/2/745.long


    Also in humans


    I just posted on another thread on reduction in levels of IL-2, TNF-alpha and IL-17 being a known feature in progressive HIV+ (as opposed to higher levels being maintained in those patients who are infected but do not get ill).
    snowathlete, Sasha and Omar88 like this.
  2. SOC

    SOC Moderator and Senior Member

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    Thanks, natasa778, I find that very interesting.

    I'm one of those with low and declining IL-17 and very low IL-2. My last immune tests showed 0.000 pg/ml IL-17 :eek: , so I guess it won't be declining any further. ;) My daughter also has very low IL-17.

    Interestingly, neither of us has gut symptoms common in ME/CFS. Not that one has to have gut symptoms to have gut epithelial barrier problems, I guess.
    aimossy likes this.
  3. Hip

    Hip Senior Member

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    natasa778

    Interesting stuff. I found some related articles on the role of IL-17 and Th17 in the intestinal barrier and the mucosal immune system:
    Th17 cells are essential for intestinal homeostasis
    Increasing Th17 Cells in the Gut May Improve the Control of HIV Growth
    Role of Th17 Cells in the Gut Mucosal Immune Barrier
    Th17 cells, HIV and the gut mucosal barrier

    However, as far as I can see, the cytokine IL-17 and the Th17 immune response are not desirable in ME/CFS, as they do a lot of bad things.

    Here are some studies on the bad effects of IL-17 and Th17:

    IL-17 and Th17 disrupt the blood-brain barrier and cause CNS inflammation:
    Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation.
    Cellular mechanisms of IL-17-induced blood-brain barrier disruption.

    Th17 cells increase coxsackievirus B3 replication in viral myocarditis (coxsackievirus B is linked to ME/CFS):
    Th17 cells contribute to viral replication in coxsackievirus B3-induced acute viral myocarditis
    The role of Th17 cells and regulatory T cells in Coxsackievirus B3-induced myocarditis
    Distinct different expression of Th17 and Th9 cells in coxsackie virus B3-induced mice viral myocarditis

    Th17 cells enhance viral persistence and block viral clearance:
    Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection

    IL-17 is linked to anxiety (in rheumatoid arthritis):
    The role of interleukin (IL)-17 in anxiety and depression of patients with rheumatoid arthritis



    I have taken an interest in IL-17 and the Th17 immune response, as a result of the significant anti-anxiety benefits I get from N-acetyl-glucosamine, a supplement which inhibits IL-17 and Th17 (ref:here).
  4. SOC

    SOC Moderator and Senior Member

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    We certainly don't want IL-17 and the Th-17 immune response to be too high any more than we want it to be too low. As with many parts of our immune function, the key is balance.

    It appears based on Dr Lipkin's statements that high IL-17 is NOT our problem, so I'm not overly concerned about the bad effects of high IL-17.
  5. Hip

    Hip Senior Member

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    Dr Lipkin I believe suggests that it might be a good idea to use immunomodulators to reduce the IL-17 response in ME/CFS patients (though he says more research is needed before this advice can be given).

    Though IL-17 is apparently only high in new ME/CFS patients; IL-17 is reduced in patients who have had the disease for 3 years or more.

    This study found that a mutation which lowers the inflammatory effects of IL-17F was found significantly less in ME/CFS patients, suggesting that this mutation might confer protection against ME/CFS, and also suggesting that the inflammatory effects of IL-17F may play a role in driving this disease.
    merylg likes this.
  6. natasa778

    natasa778 Senior Member

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    I am with SOC here, high IL-17 may well be serving some purpose - providing protection from or for something, as is the case in HIV infected.
  7. Hip

    Hip Senior Member

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    Certainly the Th17 immune response (which is activated by IL-17) does serve a purpose, and I think that's why Dr Lipkin sounds a note of caution regarding the idea of inhibiting Th17 and IL-17 in ME/CFS patients.

    So you wouldn't want to issue any general advice to ME/CFS patients to reduce their Th17 + IL-17 responses just yet.

    Though I am always quite happy to experiment on myself: there is a mad scientist on the ethics committee of my personal n = 1 study trials — me — and that mad scientist usually gives the ethical go ahead for many unorthodox or unproven treatment ideas to be tested on myself! Though I am also the first to instantly halt any such trails at any signs that hint of untoward side effects.

    In terms of the purpose of Th17: the Th17 immune response comes into play when fighting Staphylococcus bacteria (especially in the skin), Salmonella enterica in the gut, and Candida albicans. Th17 may also play a role in fighting Tuberculosis, and Borrelia bacteria, but not enough is known about this role to make any definitive statements in these cases. The discovery of the Th17 immune response is fairly new, so not that much is known about it, in comparison to the Th1 and Th2 immune responses.


    From the ME/CFS perspective, the fact that Th17 significantly increases the levels of coxsackievirus B infection in a murine myocarditis model should be cause for concern. From Dr John Chia's work, we know that ME/CFS is characterized by a persistence, smoldering enterovirus infection that, in ME/CFS patients, does not seem to go away, and is not cleared by the immune system. So the million dollar question is: what is preventing or impeding the clearance of enteroviruses like coxsackievirus B in ME/CFS patients?

    The conventional answer to this question is that the low Th1 response (antiviral response) and the high Th2 response found in ME/CFS patients act to prevent enteroviral clearance in the body, hence the use of Th2 => Th1 immunomodulators like oxymatrine, in order to boost the Th1 antiviral response, and achieve viral clearance. But as we know from Chia's research, such immunomodulators only seem to work well for a subset of ME/CFS patients. So what is blocking the effects of these Th2 => Th1 immunomodulators in the majority of ME/CFS patients that don't seem to respond to immunomodulators like oxymatrine?

    Well, what if there were other factors, such as a high Th17 response, that were also standing in the way of viral clearance? We know from the references cited above that Th17 + IL-17 act to increase enterovirus infections in a murine myocarditis model; so Th17 is acting against enteroviral clearance. It is conceivable that if you not only addressed the Th1 deficiency in ME/CFS patients, but also addressed this Th17 that may be blocking viral clearance, then you might successfully treat ME/CFS.

    So conceivably, you may have a better chance of clearing the enterovirus infections driving ME/CFS if you used both Th2 => Th1 immunomodulators like oxymatrine and Th17 suppression immunomodulators at the same time.

    Though this idea may be more appropriate in the first year or two of developing ME/CFS, where Dr Lipkin found that IL-17 is high.
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  8. Christopher

    Christopher Senior Member

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    I initially had a great response to NAG, however after repeated dosages I developed an allergic reaction when I took it. Too bad. It seemed to really calm my gut down. However due to feeling better I started drinking alcohol concurrently with taking NAG - not the brightest idea. I haven't tried it in a while so maybe it is worth trying again.

    I also had a great response to the equilibrant but a similar thing happened with the allergic reaction.
    merylg likes this.
  9. merylg

    merylg Senior Member

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  10. Christopher

    Christopher Senior Member

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    merylg I had thought of that, but I take other supplements that contain magnesium stearate and I don't have the same reaction.
    merylg likes this.

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