Prostaglandine E2

[Clodomir]

Hi,

My prostaglandine E2 is very, very high: 21,12 (normally reference range: 0,10 and 2,81)... and it was in december 2014, now I think it is worse...
I have of course a lot of inflammation... of course.
I have the "lyme protocol": Samento, Banderol, etc...
I just want to know if someone have/take THE medicine how can reduce this prostaglandine?
And why is my prostaglandine is so high

Thanks.

Clodomir

 

[msf]

I don't know the answer to the second, although I know it's a marker of inflammation, and I guess you are already taking Omega3 to reduce it, so apart from limiting Omega6, I'm not sure what else I can suggest, unless you want to use COX-2 inhibitors, which all seem to come with side effects that are not ideal for people with ME.

http://www.ncbi.nlm.nih.gov/pubmed/18610745

This article seems to suggest that Rikko-san, whatever that is, reduces PGE2, which is apparently produced by macrophages when stimulated by LPS.

 

[adreno]

how can reduce this prostaglandine

Curcumin can reduce it.

 

[msf]

Oh yeah, I forgot about that even though I've tried it - for me the effects on the gut made it not worth taking. Also, I have read that it suppresses the immune response to infection (perhaps all the COX-2 inhibitors do this).

 

[justy]

I also have this high level, and yes can feel the inflammation in my body, also have breathing issues and this is related to asthma etc as well.

Recently, since finding I have mast cell activation I have discovered that both PEG2 and il8 can be high in MSAD'S, but I don't know what to do about it...

 

[adreno]

Actually, many phenols inhibit both PGE2 and IL-8, including turmeric, egcg, pomegranate and resveratrol. They can be hard to tolerate for some, but may be worth a shot. Many of them also inhibit mast cell degranulation. GLA also reduces PGE2.

 

[Helen]

And why is my prostaglandine is so high

Hi Clodomir,
My doctor told that my elevated, and still increasing PgE2 is due to the Lyme treatment and therefore "normal".

 

[adreno]

Hi Clodomir,
My doctor told that my elevated, and still increasing PgE2 is due to the Lyme treatment and therefore "normal".

Well, it might be normal, but perhaps not optimal. From reading the following, it looks like bacteria can induce PGE2 release, which is then immunosuppresive:

Front Cell Infect Microbiol. 2013 Aug 21;3:45.

PGE(2) suppression of innate immunity during mucosal bacterial infection.

Agard M1, Asakrah S, Morici LA.

Abstract
Prostaglandin E2 (PGE2) is an important lipid mediator in inflammatory and immune responses during acute and chronic infections. Upon stimulation by various proinflammatory stimuli such as lipopolysaccharide (LPS), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, PGE2 synthesis is upregulated by the expression of cyclooxygenases. Biologically active PGE2 is then able to signal through four primary receptors to elicit a response. PGE2 is a critical molecule that regulates the activation, maturation, migration, and cytokine secretion of several immune cells, particularly those involved in innate immunity such as macrophages, neutrophils, natural killer cells, and dendritic cells. Both Gram-negative and Gram-positive bacteria can induce PGE2 synthesis to regulate immune responses during bacterial pathogenesis. This review will focus on PGE2 in innate immunity and how bacterial pathogens influence PGE2 production during enteric and pulmonary infections. The conserved ability of many bacterial pathogens to promote PGE2 responses during infection suggests a common signaling mechanism to deter protective pro-inflammatory immune responses. Inhibition of PGE2 production and signaling during infection may represent a therapeutic alternative to treat bacterial infections. Further study of the immunosuppressive effects of PGE2 on innate immunity will lead to a better understanding of potential therapeutic targets within the PGE2 pathway.

I know Buhner recommends both EGCG and Resveratrol.

 

[alex3619]

PGE2 used to be my pet topic. I have been talking and writing about this since about 1993. Its the gateway to the series two eicosanoids, and if its elevated then a whole host of eicosanoids, many of which are inflammatory, will also be elevated.

Fixing it is not easy. Ideally you would have to find the cause. To do that in ME would mean finding out what causes ME.

It can be treated however. Anything that slow the COX enzyme (cycoloxygenase) will help. Anything that modifies the substrate, which is short chain omega 6 fats (eventually its arachidonic acid) will help. Competitive inhibition helps, which works by making the enzyme do other things. This is one of the ways in which fish oil omega 3 helps. One which I suspect is a diet high in monounsaturated fat might help. This fat might bind to the enzyme. Both aspirin and paracetamol have an impact. So does neurofen but I think the mechanism is different from what I have studied and I am not sure what impact it will have.

Release of arachidonic acid is the big thing. Alcohol releases it, low cortisol increases it. Substances like peroxynitrite and other inflammatory substances can increase its utilization.

Here are some caveats though. Arachidonic acid is an essential fatty acid. What that means is that without it you will die. You cannot just completely stop all omega 6 fats. When they used Vioxx the shut down arachidonic acid utilization, which shuts down an entire essential hormone tree.

I strongly suspect most of us have over-use of arachidonic acid. Many of us don't eat much of it though (its mainly in meat fat) or cannot make enough (e.g. low glutathione or salicylate intolerance) and so are deficient, as any we eat is rapidly used. If its high then its possibly a supply issue as well. You are consuming or making too much.

Evening primrose oil and borage oil can wind up as arachidonic acid. Butter, cheese, most meats but particularly fat and organ meats, are all high in arachidonic acid.

One last point. In theory its possible you are not over-using it, and that something is blocking its use. I know of no mechanisms that can do so but cannot rule out the possibility.

 

[alex3619]

From reading the following, it looks like bacteria can induce PGE2 release, which is then immunosuppresive:

PGE2 is usually considered immunoactive, not suppressive. I need to read this article, I suspect what is happening is there is increased inflammation and the bacteria are using it to bypass barriers that normally prevent them spreading, or alternatively the localized PGE2 responses might be different in these specific tissues.

What can cause confusion here is PGE2 is a precursor of other hormones.

On the subject of LPS, lipopolysaccharide, its what is called a super antigen. It makes the body systems go nuts. I do not fully understand it but then I am not sure anyone does. I always meant to continue investigating the literature on this but I am not well enough to do that right now.

PS I love my resveratrol. Its got sooooo many good effects and I can tell the difference when I am on it.

 

[Thinktank]

@Clodomir, the elevated PGE2 is probably caused by an increased die-off reaction. The LPS from mostly gram negative bacteria provoke PGE2 release and other proinflammatory substances. PGE2 can cause inflammation directly to the hypothalamus, thus that's another reason why you are feeling crappy.
Have your proinflammatory cytokines been measured as well this time? Any change?

P.s. My PGE2 is over 40 and ever increasing. After 6 measurements spanning a period of 1.5 years time i have noticed a trend between the level of PGE2 and neuroinflammation.

 

[Clodomir]

Hi everyone,

Thanks a lot for all this information. KDM will give me something but I suspect it will be AINS.... (indometacin in suppository... yeah!!!) Not sure: I will have his protocol next week.
I already try: IV injection, pills, drops, muscular injection, sub cutaneous injection, liquid, and now... a little rocket, just before going to sleep...
Where do you buy your resveratrol? Is there a brand better than an other? I will maybe try.
And Yes my IL-8 are very High also, and KDM say that it is normal...
I am feeling better now than a year before, but now, I have the feeling not to progress anymore (I am a impatient person...)
The only thing, I am happy about is that now I am a tick Killer, with all the stuff in my blood (samento, cumanda, etc...) I have ask KDM, what could happen if a tick bite me, he says He will die!!!!

Have a good day

Clodomir

 

[msf]

Haha, I'm starting to appreciate Belgian humour...I'm glad you are seeing slow progress, Clodomir, hopefully it will pick up the pace soon!

 

[alex3619]

Where do you buy your resveratrol? Is there a brand better than an other?

I buy an Australian brand. The key thing here, from my persective, is the trans resveratrol content. Some of us tolerate it sourced from Japanese knotweed, but its safer to source it from red grapes.

I found that I need a 600mg dose of trans resveratrol, but only twice a week. Lower doses more often do not work for me.