IL-12

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IL-12

Postby dignan » Tue May 31, 2005 9:44 pm

IL-12 seems to implicated in MS, and this abstract refers to agents to control IL-12 production. I recently read something in Pubmed about quercetin (found in apples among other places I think) having an effect on IL-12. Anybody know of any other drugs / supplements that could have a beneficial effect on IL-12 for PwMS?


Regulatory mechanisms and their therapeutic implications of interleukin-12 production in immune cells.

Kang BY, Kim E, Kim TS.

Department of Pharmacy, College of Pharmacy and Research Institute of Drug Development, Chonnam National University, 300 Yongbong-dong, Buk-ku, Gwangju 500-757, South Korea.

Studies with neutralizing anti-interleukin (IL)-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular microorganisms. However, IL-12 also appears to play a central role in the pathogenesis of autoimmune diseases such as multiple sclerosis or rheumatic arthritis. Therefore, it is crucial to understand how IL-12 is produced and its production is regulated at the molecular level. IL-12 production is differentially regulated through multiple pathways, which can be classified as follows: nuclear factor-kappaB (NF-kappaB) and other transcription factors, p38 mitogen-activated protein (MAP) kinase, cyclic adenosine monophosphate (cyclic AMP)-modulating molecules, cell membrane ion channels and pumps, nitric oxide (NO), and receptors. In this review we describe the regulatory mechanisms of IL-12 production in immune cells and also some agents to control IL-12 production for the treatment of immune-related diseases.

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Postby MacGyver » Wed Jun 01, 2005 4:16 am

Dignan wrote:Anybody know of any other drugs / supplements that could have a beneficial effect on IL-12 for PwMS?


Inosine, used in recent trials by for example G. Toncev, Hooper et.al. to raise serum uric acid levels in MS patients, does according to the study below also inhibit IL-12 production. The original theory behind using inosine to treat MS was that inosine is rapidly converted to uric acid, which is supposed to scavange peroxynitrite (or it's metabolites). I don't know how rapidly inosine is broken downby the human body, maybe it is so fast that it's properties as an immunomodulator are totally irrelevant.

The company Inotek has developed a substance with inosine's properties preserved, but it's half-time is prolonged. I don't think it is in trial or even planned to be in trial yet though(?)

To read more take a look at this paper:
Inosine inhibits cytokine production...
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Postby dignan » Wed Jun 01, 2005 8:07 am

Interesting. I have heard about inosine trials for MS patients, but I didn't know anything more than it is supposed to be a uric acid precursor and they know some PwMS are low in uric acid, at least during relapse. There was a trial somewhere in central/eastern Europe on inosine -- is the group who wrote this paper the group that did the trial?
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Re: IL-12

Postby NHE » Thu Jun 02, 2005 3:42 am

dignan wrote:Anybody know of any other drugs / supplements that could have a beneficial effect on IL-12 for PwMS?

I'm not sure about IL-12, but there are several supplements that inhibit NF-kB.
Some of these include...
- Epigallocatechin gallate (EGCG) from green tea
- Lipoic Acid
- Curcumin from turmeric

There are likely others as well, but I can't recall them at this time.

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Postby MacGyver » Thu Jun 02, 2005 4:44 am

Dignan wrote:There was a trial somewhere in central/eastern Europe on inosine -- is the group who wrote this paper the group that did the trial?

No they are not connected as far as I know. Szabo et al. have published several reports regarding inosine and autoimmunity (pubmed search with "Szabo[auth] inosine" should render some interesting hits). The Yugoslavian group you are referring to, led by Dr. Gordana Toncev, have so far presented results focusing on the inosine-uric acid-antioxidant trail.
The latest trial by the yugoslavians was highlighted by the NMSS this spring:
Gordana Toncev, MD (Clinical Hospital Center Kragujevac, Yugoslavia) and colleagues studied the effectiveness of inosine in secondary-progressive and relapsing-remitting MS. They administered oral inosine to 32 people daily for 24 months, and compared the results to 32 untreated controls. People treated with inosine had no adverse effects, lower rates of MS relapses, and lower scores on the EDSS, a measure of disease activity (Abstract #P06.091, American Academy of Neurology [AAN] Annual Meeting, 2004). Further study is needed to confirm these early results.

Sofar we have only seen the poster presentation, but the final report is to be published during 2005. It will be very interesting to read, especially when similiar studies are still missing. An american study at the University of Pennsylvania have had problems recruiting patients(!) and is still not finished though it was planned to have finished in 2004.
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Postby dignan » Thu Jun 02, 2005 9:15 am

Thanks for all the info. I've been waiting for that University of Pennsylvania study. I hope it's not too far from completion. It seems to me that the supplements that have the most effort behind them, in terms of discovering their efficacy for MS, are alpha lipoic acid and inosine.

For all the studies that have been done about omega3 and vitamin D, I'm not aware of clinical trials going on for either of them right now. I know there is one trial of B12 with interferon and one of NAC with copaxone -- and that's all I know of for trials with non-prescription substances. Am I missing anything?
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