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Effects of histamine on Th1/Th2 cytokine balance

Discussion in 'Mast Cell Disorders/Mastocytosis' started by nanonug, May 6, 2012.

  1. nanonug

    nanonug Senior Member

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    I am convinced that histamine plays a strong role in mediating many of the symptoms experienced by PwME. It is also more or less accepted that in ME, there is a shift from Th1 to Th2 immune response. Interestingly enough, histamine also appears to be associated as the following abstract shows:

    Effects of histamine on Th1/Th2 cytokine balance

    Excerpt:

    "Histamine enhances the secretion of Th2 cytokines such as IL-4 (interleukin-4), IL-5, IL-10 and IL-13 and inhibits the production of Th1 cytokines IL-2 and IFNgamma (interferon-gamma) and monokine IL-12."
    Flower1978 likes this.
  2. adreno

    adreno 3% neanderthal

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    Right, histamine is very inflammatory.
  3. mellster

    mellster Marco

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    So low-dose anti-histamine therapy would make for a nice self-experiment? Anything know about the kind of anti-histamines needed, broad spectrum or something as simple as H2 blockers like famotidine? Or simple allergy medicine like benadryl? Thx & cheers
  4. adreno

    adreno 3% neanderthal

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    I would like to get my hands on an H4 antagonist:


    The role of histamine H4 receptor in immune and inflammatory disorders.

    Zampeli E, et al.

    Br J Pharmacol. 2009 May;157(1):24-33. Epub 2009 Mar 20.

    Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

    Abstract

    Since its discovery at the beginning of the 20th century, histamine has been established to play a pathophysiological regulatory role in cellular events through binding to four types of G-protein-coupled histamine receptors that are differentially expressed in various cell types. The discovery, at the turn of the millennium, that the histamine H4 receptor is largely expressed in haemopoietic cells as well as its chemotactic properties designate its regulatory role in the immune system. H4 receptors modulate eosinophil migration and selective recruitment of mast cells leading to amplification of histamine-mediated immune responses and eventually to chronic inflammation. H4 receptor involvement in dendritic cell activation and T cell differentiation documents its immunomodulatory function. The characterization of the H4 as the immune system histamine receptor directed growing attention towards its therapeutic exploitation in inflammatory disorders, such as allergy, asthma, chronic pruritus and autoimmune diseases. The efficacy of a number of H4 receptor ligands has been evaluated in in vivo and in vitro animal models of disease and in human biological samples. However, before reaching decisive conclusions on H4 receptor pathophysiological functions and therapeutic exploitation, identification of genetic polymorphisms and interspecies differences in its relative actions and pharmacological profile need to be addressed and taken into consideration. Despite certain variations in the reported findings, the available data strongly point to the H4 receptor as a novel target for the pharmacological modulation of histamine-transferred immune signals and offer an optimistic perspective for the therapeutic exploitation of this promising new drug target in inflammatory disorders.

    PMID 19309354
  5. adreno

    adreno 3% neanderthal

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    The histamine H? receptor: targeting inflammatory disorders.

    Walter M, et al.

    Eur J Pharmacol. 2011 Oct 1;668(1-2):1-5. Epub 2011 Jul 3.

    Johann Wolfgang Goethe University, Institute of Pharmaceutical Chemistry, Biocenter, ZAFES/LiFF/CMP/ICNF, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.

    Abstract

    The discovery of the histamine H(4) receptor has added a new chapter to the century of extensive biogenic amine research. The human histamine H(4) receptor is mainly expressed in cells of the human immune system (e.g. mast cells, eosinophils, monocytes, dendritic cells, T cells) and mediates several effects on chemotaxis with numerous cell types. The distinct expression pattern and the immunomodulatory role highlight its physiological relevance in inflammatory and immunological processes. Inflammatory conditions, e.g. allergy, asthma and autoimmune diseases, were for a long time thought to be mainly mediated by activation of the histamine H(1) receptor subtype. However, in the treatment of diseases as chronic pruritus, asthma and allergic rhinitis the use of histamine H(1) receptor antagonists is unsatisfying. Selective H(4) receptor ligands and/or synergism of histamine H(1) and H(4) receptor modulation may be more effective in such pathophysiological conditions. Promising preclinical studies underline its role as an attractive target in the treatment of inflammatory and autoimmune disorders. Meanwhile, first histamine H(4) receptor antagonist has reached clinical phases for the treatment of respiratory diseases.

    PMID 21741967
    Merry likes this.
  6. roxie60

    roxie60 Senior Member

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    Is there a test that shows a person's H4 histamine receptor status? can it show improvement w/ some type of treatment? Could this be another marker?
  7. nanonug

    nanonug Senior Member

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    I guess it would, if you could antagonize all four histamine receptors. I don't think that's currently possible, though.

    There is currently no way to antagonize all four receptors. H1 and H2 blockers exists. However, I am not a fan of antagonizing just H2. This would result in less stomach bad, which is bad in itself, and result in higher overall levels of histamine, due to the lack of feedback inhibition from hydrochloric acid.

    Best bet is to find what is causing high histamine levels in the first place and address it.
  8. nanonug

    nanonug Senior Member

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    To my knowledge, there isn't.
  9. nanonug

    nanonug Senior Member

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    Awesome news!
  10. adreno

    adreno 3% neanderthal

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    But rather than blocking histamine receptors, preventing it's release would be preferable. Maybe Th2 -> Th1 shifters, or mast cells stabilizers could be helpful.
  11. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    I also wait for a H4 antagonist.
  12. Overstressed

    Overstressed Senior Member

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    Hi,

    some while ago I had read an interesting report on MS, and the authors of that report concluded that histamine protects the brain, and that people with MS showed decreased levels of histamine. If I can find that report, I'll post it here, right away!

    Best regards,
    OS.
  13. adreno

    adreno 3% neanderthal

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    I think it's important that we differentiate between central and peripheral histamine. AFAIK, central histamine is not involved in allergic reactions.
  14. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    doxepine has been shown to be helpful to cfs/me and is used mainly for sleep and calming the nervous system down but i wonder if some of its effects are because of its antihistamine effects. I have read somewhere that it is the strongest antihistamine around, but dont quote me.

    cheers!!!
  15. nanonug

    nanonug Senior Member

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    According to Wikipedia:

    "Doxepin also has antagonistic effects at a variety of receptors:

    Extremely strong: H1, H2 (Ki = 0.7 nM)
    Strong: 5-HT2, ?1-adrenergic, mACh
    Moderate: 5-HT1, local anesthetic action."
  16. adreno

    adreno 3% neanderthal

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    All of the TCAs, and mirtazapine have antihistaminergic properties. Centrally acting histamine antagonism will cause somnolence. The 1st generation antihistamines also crosses the BBB, and so cause sedation.

    It is also speculated that some of the positive effects of TCAs, especially amitriptyline, are due to mast stabilizing properties. Unfortunately, it has affinity for so many receptors that it is a very dirty drug.
  17. adreno

    adreno 3% neanderthal

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  18. DANEL

    DANEL

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    hi,
    i am clueless about this but wondered 2 things, i have ben reading about mast cell. It says mold and mercury are triggers of mast cell, which i have and addressing both, the mercury with dr cutler's protocol DMPS and ALA frequent dose chelation and mold, by as safe a place as i can find, cms, methy supplements, BBB compromise supp, and proteolytic enzymes adding "killing herbs" then a binder to eliminate the toxins, sauna.

    i got a script for ketotifen. it is for mast cell, i have it compounded, b/c you can't purchase in US except by compounded
    don't know if it is helping or not.
    do you know if it bloks only h2 or both h1 and 2


    I have been diagnosed with high stomach acid not low through a upper endo scope and by a biofeedback person.

    wonder what your thoughts are,

    denise
    thanks
  19. adreno

    adreno 3% neanderthal

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    Denise, as far as I can tell, ketotifen blocks only H1 (in addition to being a mast cell stabilizer).
  20. DANEL

    DANEL

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    hey
    thanks

    i am having a huge problem with BBB compromise, almost anything i take as supplements, esp b's, smell, sniff, causes me sedation, weakness, in muscles, brain fog, in ability to think, headache nausea and have MCS which it seems like it is the same as MCS. i know MCS has also to do with methylation and liver phase 1/2

    so even though the keto tested very good for me, it causes brain fog and stupidity;) same with CSM for mold, but do it anyway to release bio/neurotoxins

    i am so wildly sick, with all the things mentioned about.

    so my body may test well and the bio says i need this, but it doesn't mean i can tolerate it b/c of something else like BBB compromise.

    so i need to fix the bbb with a list of supplements i found, mercury, detox all toxins with things mentioned above
    sound simple, but NOT
    thanks
    denise

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