Immunomodulatory and neuroprotective effects of inosine

[heapsreal]

Thought this might be of interest



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.

 

[SOC]

Thought this might be of interest

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.....

 

[heapsreal]

yes it seems to have good antioxidant and anti inflammatory effects as well as improving nk and T cells.

 

[Ema]

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.

 

[heapsreal]

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.

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

 

[Ema]

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

My NK cells have always, strangely, been good.

 

[heapsreal]

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!!

 

[jeffrez]

Inosine enhances mast-cell degranulation,

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?

 

[SOC]

My NK cells have always, strangely, been good.

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.

 

[Ema]

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.

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.

 

[Ema]

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?

 

[Ema]

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?

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?

 

[heapsreal]

[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

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?

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

 

[Ema]

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?

I have high histamine and have not noticed any worsening of symptoms with inosine.

 

[adreno]

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.

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]

I have high histamine and have not noticed any worsening of symptoms with inosine.

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.

 

[Ema]

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?

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

 

[SDSue]

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.

 

[Ema]

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.

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.

 

[Ninan]

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.

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.