Re: IL-15, A potential therapeutic agent in CFS?

[Guest guest]

my apologies, forgot to add this last part!:

a quote from the study: " These results clearly indicated that

autocrine IL-15-mediated activation of IL-15R is essential for

MICA/B (the costimulators) expression induced by type I IFN on DC and

strongly support the idea that impaired production of IL-15 is

responsible for the hyporesponsiveness of HCV-DCs to type I IFN in

terms of MICA/B expression as well as the ability to activate NK

cells. "

here is the abstract:

Autocrine/paracrine IL-15 that is required for type I IFN-mediated

dendritic cell expression of MHC class I-related chain A and B is

impaired in hepatitis C virus infection.

Jinushi M, Takehara T, Tatsumi T, Kanto T, Groh V, Spies T, Suzuki T,

Miyagi T, Hayashi N.

Osaka University Graduate School of Medicine, Department of Molecular

Therapeutics, Suita, Osaka, Japan.

We previously reported that monocyte-derived dendritic cells activate

resting NK cells by expressing MHC class I-related chain A and B

(MICA/B), ligands for NKG2D, in response to IFN-alpha, but the MICA/B

expression was severely impaired in patients with chronic hepatitis C

virus (HCV) infection. In the present study, we examined induction of

MICA/B on DCs by various innate cytokines and found that DCs from

either healthy donors or HCV-infected individuals, upon IL-15

stimulation, express MICA/B and can activate NK cells, which is

solely dependent on MICA/B-NKG2D interaction. Of interest is the

finding that IL-15- and type I IFN-mediated induction of MICA/B in

healthy donors is completely inhibited when DCs are incubated in the

presence of anti-IFN-alpha/betaR or anti-IL-15Ralpha, respectively,

suggesting interdependent roles of these cytokines in MICA/B

expression. Indeed, DCs produced IL-15 in response to type I IFN,

whereas they directly produced IFN-beta, in response to IL-15, which

was followed by the production of IFN-alpha. In HCV-infected

individuals, type I IFN-mediated production of IL-15 was virtually

absent, but IL-15-mediated production of type I IFN was not

compromised, which is consistent with the distinct ability of these

cytokines to induce MICA/B in these patients. The present study

demonstrates that IL-15 and type I IFN lead to DC expression of

MICA/B and subsequent DC activation of NK cells, which is critically

dependent on each other's autocrine/paracrine effect, and suggests

that impaired IL-15 production is one of the mechanisms of the

aberrant response of DC to type I IFN in HCV-infected patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=PubMed & list_uids=14607946 & dopt=Abstract

[Guest guest]

Thanks for posting this. Is IL-15 available to the public?

Bob

[Guest guest]

> Thanks for posting this. Is IL-15 available to the public?

>

> Bob

Hey Bob H!

Nice to hear from you. Hope you are doing okay. Unfortunately IL-15

is only avaliable is only avaliable to the public with Stat1 (my

understanding)... in other words, not to us. My understanding is that

if anyone has a prayer of getting it (as of today) such a person

would have to have a doctor who was: at a major university, actively

interested in CFS reserach, with a background in immunology,

geniunely concerned and caring for his/her CFS patients, and with

quite an intrepid streak (how many doctors like that are there in the

world?)

I was posting this mainly because (as far as I can tell) it seems a

very logical and direct extension of De Meirleir's findings and so

just to add to people's knowledge, ... a good thing in itself. In the

abstract this study, if applicable to CFS as I believe, also

reinforces the evidence that the cellular immunity should be

deficient in CFS. People could use this in their treatment plans,

which is why I mentioned Zadaxin...

(http://www.sciclone.com/products/zadaxin.shtml).

If you are interested you could post a message to a asking about

any questions you have about Zadaxin, since she knows a lot more than

me. It is not (quite yet) avaliable in the US however. Something else

I am investigating, of which you might be interested, is Low Dose

Naltrexone. I don't know enough yet to gauge how strong the Science

is behind the theory of why it works or even give my own opinion, but

it supposedly raises NK cells, which I believe should probably also

help cellular immunity in CFS. There is also a website for

information about it: www.low dose naltrexone.org .

My best regards,

" " Naltrexone (Low Dose Naltrexone)

The following explains Low Dose Naltrexone (also known as LDN) from a

layperson's perspective that everyone should be able to understand.

Please note that we are not medical doctors, and that there is no

formal proof of the following statements; they are merely informed

hypotheses. You should always do your own research and consult with

your doctor before undertaking any medical treatment.

The simple explanation:

Naltrexone is an FDA approved drug (1984) that was originally

intended to treat people suffering from opium (e.g., heroin)

addiction. It treated these addictions by blocking the " pleasant "

effects from the drug, so addicts who took it did not get " high "

anymore.

How does it block the " high? " There are receptors in our brain that

an opioid like heroin would use to get into the cell and do its deed.

Naltrexone blocks those receptors, so the heroin can't have an

effect. Think about it like a puzzle piece-- some brain cells have a

piece that accepts opium and its derivatives, and the Naltrexone

simply matches that piece. When the heroin floats around, it has no

where to go.

OK, that's all well and good, but what relevance is there to Multiple

Sclerosis?

Well, those opiod receptors in our brains are not JUST for receiving

drugs like heroin-- our bodies actually produce opiods every day,

among other things, we produce a set of hormones called endorphins.

So if you were to take Naltrexone, you would actually block the

reception of something your body produces. These hormones, as it

turns out, play a very important part in controlling the immune

system. Keep this in mind for what we'll talk about below.

The FDA-approved dosage for heroin addicts was 50 milligrams per day.

This ensured that those receptors were blocked all day and there was

no chance that any heroin could connect with a cell and give the user

a " high. "

BUT a medical doctor named Dr. Bihari found that if you give someone

a much lower dose, say THREE milligrams instead of 50, you would not

block the receptors all day, but just for a couple of hours. After

that, everything would function as normal.

But the human body is funny-- when you block something, it often

responds by producing more. In other words, if you were to take

Naltrexone at a low dose (Low Dose Naltrexone, even!) you would block

the receptors for a couple hours. The body would notice that it was

not receiving the endorphins it produced, so it would think " Since

they're not getting through, I must not be producing enough-- turn it

up! " The gland responsible for producing the endorphins, called the

pituitary, would respond by producing significantly more. Not enough

to cause any problems, but enough to make a difference.

So how can this all matter for Multiple Sclerosis? Remember how we

discussed above that the endorphins actually regulate the immune

system? Well, in Multiple Sclerosis, the immune system is

malfunctioning-- it's attacking it's own body. Anything that helps

regulate, control, and tame the immune system could potentially have

a positive effect on MS. And that's exactly what some people who take

LDN report-- a halt of the progression of the disease, and even some

improvement in symptoms.

Adding some scientific validity are studies that show that in MS

patients, the pituitary gland (which produces endorphins) shrinks as

the disease progresses. This shrinkage can be assumed to correspond

with less endorphin production, though the link is not concrete. The

million dollar question is: is the pituitary gland shrinking BECAUSE

of the MS, in which case fixing the pituitary is more like treating a

symptom rather than the cause, OR is the pituitary smaller in people

who have multiple sclerosis and could potentially be a, if not the,

cause of the disease in the first place? In other words, is a

shrunken pituitary a cause of MS or is it an effect? If it's a cause,

making up for the lower endorphin output by taking something like LDN

could have significant positive implications.

There is a catch to all of this-- there are no formal, clinical

trials on taking low dose naltrexone for multiple sclerosis (though

one just got underway for Crohn's disease--remarkable because Crohn's

is an autoimmune disorder like MS). All there is is speculation, a

few doctors backing it, and most remarkably, many positive

testimonials from patients.

If you would like to copy and paste this article, please credit the

source:

This Is MS Unbiased Multiple Sclerosis Community

http://www.thisisms.com " "

[Guest guest]

Something else

> I am investigating, of which you might be interested, is Low Dose

> Naltrexone.

, once again I appreciate the information. I always keep an open-

mind about things regarding CFS. I am presently on my 8th day of the

Marshall Protocl and I am very encouraged so far. I know several

people who have been on it for over 6 weeks and they keep

progressing. From everything I have read, Saecoidosis could be a

(the) problem with PWC's.

Bob H.

[Guest guest]

I am presently on my 8th day of the

> Marshall Protocl and I am very encouraged so far. I know several

> people who have been on it for over 6 weeks and they keep

> progressing. From everything I have read, Saecoidosis could be a

> (the) problem with PWC's.

>

> Bob H.

its np. Best luck to you on the Marshall Protocol!