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Immunomodulatory and neuroprotective effects of inosine

Discussion in 'Other Health News and Research' started by heapsreal, Oct 24, 2013.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Thought this might be of interest:thumbsup:



    http://www.inotekcorp.com/publications/pdf/ipcpub306.pdf



    Adenosine has been considered as a potential immunomodulatory

    and neuroprotective agent for 30 years.

    Inosine, a major degradation product of adenosine,

    was thought originally to have no biological effects.

    However, recent studies demonstrate that inosine has

    potent immunomodulatory and neuroprotective effects.

    Inosine enhances mast-cell degranulation, attenuates

    the production of pro-inflammatory mediators by

    macrophages, lymphocytes and neutrophils, and is protective

    in animal models of sepsis, ischemia–reperfusion

    and autoimmunity. Inosine preserves the viability

    of glial cells and neuronal cells during hypoxia, and

    stimulates axonal regrowth after injury. The biological

    actions of inosine might involve effects on adenosine

    receptors, poly(ADP-ribose) polymerase and cellular

    energy levels. In this article, we review recent observations

    indicating that it might be possible to exploit

    inosine therapeutically for the treatment of tissue

    damage caused by inflammation and ischemia.
  2. SOC

    SOC Moderator and Senior Member

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    Interesting, indeed! I haven't considered inosine because I have normal NK cell number and function, but now I'm wondering if it might still be worth trying for its other effects.....
  3. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    yes it seems to have good antioxidant and anti inflammatory effects as well as improving nk and T cells.
    Emootje likes this.
  4. Ema

    Ema Senior Member

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    When I had my methylation panel done, adenosine was one of the things that was above range. However, my uric acid level is below range.

    I wonder what process transforms adenosine into uric acid because it would appear that I don't do it very well.

    Also, I think this is one of the reasons caffeine works so well for me - it temporarily displaces adenosine. Adenosine causes fatigue.

    I've taken inosine now for about 6 months and my uric acid levels have come into range so I believe that part works for me anyway.
    L'engle, August59 and heapsreal like this.
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Have u seen any other labs improve such as nk numbers or function since on inosine?
  6. Ema

    Ema Senior Member

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    My NK cells have always, strangely, been good.
    heapsreal likes this.
  7. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    in the past when i have used inosine i have noticed that it has improved my joint pains, maybe reducing inflammation??
    After my next lot of testing to see if ahcc increases nk numbers i will then add inosine to the mix and see what happens??

    cheers!!
    SickOfSickness likes this.
  8. jeffrez

    jeffrez Senior Member

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    Wouldn't we want to prevent mast cell degranulation? I thought mast cell degranulation is what releases histamine and other nasties?

    Have always been interested in taking inosine since Cheney talked about it as an immune modulater - have a bottle that's been sitting in my cabinet for years, lol - but was afraid of reports of gout from taking too much. Now seeing it enhances degranulation makes me even more wary. Do you have allergies, Heaps, and did you notice any increased histamine effects from taking inosine?
  9. SOC

    SOC Moderator and Senior Member

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    Mine, too. What are you taking inosine for? I thought it was primarily for NK cell dysfunction, although I see I may have been wrong. :p
  10. Ema

    Ema Senior Member

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    I read that inosine was a good way to raise uric acid levels. Low uric acid levels are often found in MS (not that I think I have that but I do think that there are similarities). And raising the uric acid level is supposed to make episodes shorter in MS. I figured it was worth a try along with the immunomodulatory effects.

    I can't say I've noticed anything one way or the other though even though my uric acid levels are now in range.
  11. Ema

    Ema Senior Member

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    Look at this!

    From Wikipedia:

    "Some mutations in the gene for adenosine deaminase cause it not to be expressed. The resulting deficiency is one cause of severe combined immunodeficiency (SCID).[7]Deficient levels of ADA have also been associated with pulmonary inflammation, thymic cell death, and defective T-cell receptor signaling.[8][9]"

    Somehow my immune deficiencies make more sense. I wonder if this gene can be found on 23andme?
    SOC likes this.
  12. Ema

    Ema Senior Member

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    Wikipedia also says carriers are generally not affected.

    I wonder if that is true or if they are just not as severely affected so as to be noticed?
    SOC likes this.
  13. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    [q
    te="jeffrez, post: 398859, member: 677"]Wouldn't we want to prevent mast cell degranulation? I thought mast cell degranulation is what releases histamine and other nasties?

    Have always been interested in taking inosine since Cheney talked about it as an immune modulater - have a bottle that's been sitting in my cabinet for years, lol - but was afraid of reports of gout from taking too much. Now seeing it enhances degranulation makes me even more wary. Do you have allergies, Heaps, and did you notice any increased histamine effects from taking inosine?[/quote]
    Im g
    Im going to use inosine to try and increase nk numbers and function as well as it being a peroxynitrate scavenger.
    I dont have alot of issues with allergies.
    I suppose every substance has positive and negative issues, we just have to way them all up.
    From what I have read theres more positives then negatives.

    Cheers
    jeffrez likes this.
  14. Ema

    Ema Senior Member

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    I have high histamine and have not noticed any worsening of symptoms with inosine.
    jeffrez likes this.
  15. adreno

    adreno 3% neanderthal

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    LOL, I feel exactly the same way, and have also had a bottle of inosine sitting in my cabinet for years :)

    I have allergies and can do without any more mast cell degranulation.
    jeffrez likes this.
  16. jeffrez

    jeffrez Senior Member

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    I didn't notice any, either, when I took it for a short while (before the gout fear got to me). And I have really bad allergies.

    All I keep seeing in reference to the process of mast cell degranulation is that it's thereby having anti-inflammatory/anti-PI cytokine effects. Seems counterintuitive, so I guess I'm missing something. ?

    e.g.:

    Blood. 2003 Dec 15;102(13):4472-8. Epub 2003 Aug 28.
    Differential requirement for A2a and A3 adenosine receptors for the protective effect of inosine in vivo.
    Gomez G, Sitkovsky MV.
    Source
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N311, 10 Center Dr-MSC 1892, Bethesda, MD 20892-1892, USA.

    Abstract
    Inosine is an endogenous nucleoside with immunosuppressive properties that is known to inhibit the accumulation of proinflammatory cytokines and protect mice from endotoxin-induced inflammation and lung tissue damage. There are no known receptors specific for inosine, but A3 adenosine receptors (A3Rs) have been shown to bind inosine, resulting in mast cell degranulation and increased vascular permeability. The present study specifically addresses the requirement for A2aR and/or A3R for the protective effect of inosine in 2 experimental in vivo models of inflammatory disease. The data show that A3R is essential for protection against ConA-induced fulminant hepatitis since only A3R-expressing mice were protected by inosine whereas wild-type and A2aR-deficient mice exhibited severe liver damage even after administration of inosine. In addition, we show in a model of LPS-induced endotoxemia that inosine protected both A2aR-/- and A3R-/- mice from inflammation, but not A2aA3R double-null mice, indicating that in this model both A2aR and A3R were used by inosine. Thus, we demonstrate that A2a and A3 adenosine receptors are differentially utilized by inosine for the down-regulation of tissue damage under different inflammatory conditions in vivo.
    Valentijn likes this.
  17. Ema

    Ema Senior Member

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    It looks like adenosine deaminase can be tested at Quest.

    Although it says that it is a marker when high for inflammation and chronic infection...so I'm not sure that my theory that it is low holds any water in that case.

    But why else would adenosine be high and uric acid be low if not for a pathway that didn't function optimally?

    It looks like an asthma/COPD drug called theophylline can be used to block adenosine but it also looks kind of tricky in terms of side effects.

    http://en.wikipedia.org/wiki/Theophylline

    Ema
  18. SDSue

    SDSue Florida

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    INIM is starting me on inosine due to preliminary immune results. (Don't know specifics yet, but told to start it now rather than waiting til face-to-face visit)

    Are any of you still taking it? Results? Warnings?

    I'm a little leery as both my siblings (males) have recently had gout. Has anyone developed gout with inosine use?

    Thanks so much.
  19. Ema

    Ema Senior Member

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    I took inosine for about a year. I didn't have any issues with it at all in terms of side effects.

    I pulsed it according to the Cheney protocol but I'm not sure if that is the recommended way to take it anymore?

    I had lower than range uric acid levels (high uric acid levels are indicative of gout). This is typical for some reason for many with chronic diseases like MS or ME/CFS. Taking inosine brought my uric acid levels up into the optimal range quite quickly.

    I would find out what your uric acid level is prior to treatment and so you can monitor for the risk of gout if you are concerned.
    SDSue likes this.
  20. Ninan

    Ninan Senior Member

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    How long did you take it before you noticed any results. If you did, that is. I've taken inosine a couple of times but never regularly. Never noticed anything at all.

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