Glucocorticoids - Prednisone, Entocort and Budesonide

[mle_ii]

Ok, here's a bit of info on inhibiting the TH1 immune response. For those who haven't read what I wrote elsewhere, this is the reaction that takes place during Microscopic Colitis.

And inhibiting the TH1 response is what Prednisone, Entocort and Budesonide all do. All of these steroids are classified as Glucocorticoids. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-γ, the most important of which is the IL-2. Without TNF-γ and IL-2 the TH1 response cannot occur.

What is strange to me is that the normally occuring Glucocorticoid produced by the body is Cortisol. What!?!?? How can this be? It seems like when we get stressed we get more symptoms. Well cortisol does indeed inhibit the immune system, and thus can inhibit the TH1 response.

So this has me wondering why things seem worse for us when we are stressed. Seems like the bodies form of steroids for controlling the immune system would work just fine.

Perhaps the receptors are ignoring or have been hampered? Perhaps we don't produce enough cortisol to stop or slow down the immune response?

I also stumbled across information about the production of cortisol, part of the path to making this is cholesterol. Are our cholesterol levels increased because we aren't making enough cortisol? It seemed a few here have higher than "normal" levels, me included. Though I'm only slightly higher in total, I have good levels of all, but combined it ends up being greater than 200.

What is even stranger is that I'm finding studies that show where cortisol closes tight junctions and other studies where it opens them.

What also blew me away in recent research about tight junctions is that the omega3 fats (you know the good ones, fish oil as an example) open tight junctions, whereas the omega6 fats (the ones we consume too much of mainly vegetable oils) close tight junctions. Madness I tell you.

Mike

[mle_ii]

Ok, here's the reason cortisol won't work.
http://www.ncbi.nlm.nih.gov/entrez/quer ... s=15066020

It appears that stress and the chemicals it produces slows down small bowel motility and increases large bowel motility. So it slows down digestion but speeds up emptying your colon.

[starfire]

Mike,
I'm tipping my hat to you - you sure are wading through some confusing "stuff" and sticking to it besides. I wish you GOOD LUCK in figuring it all out. (and don't forget to tell us cause I'd drown in all that research).

Love, Shirley

[mle_ii]

Mike,
I'm tipping my hat to you - you sure are wading through some confusing "stuff" and sticking to it besides. I wish you GOOD LUCK in figuring it all out. (and don't forget to tell us cause I'd drown in all that research).

Love, Shirley

Thanks, I actually enjoy reading and researching this stuff. In fact I just found the following that was interesting...

[mle_ii]

And here we go again. While reading about the MAP virus (the one folks think is associated with Chrons Disease) and it's possible association with Type 1 diabetes I came across another immune inhibitor. And we've talked about this before haven't we...

And it's Vitamin D. I had always wondered why it seemed to be inversly associated with various autoimmune diseases. Guess I should have ventured there more.

Here's just one article, there are many more.
Intervention in autoimmunity: the potential of vitamin D receptor agonists.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum

Vitamin D receptor (VDR) agonists are well known for their capacity to control calcium metabolism and to regulate growth and differentiation of many cell types. More recently, it has become clear that VDR agonists possess immunoregulatory properties and, in particular, pronounced pro-tolerogenic activities. VDR agonists can act directly on T cells, but DCs appear to be their primary targets. The capacity of VDR agonists to modulate DC and T cell functions is mediated by VDR expression in both cell types and by the presence of common targets in their signal transduction pathways, such as the nuclear factor NF-kappaB that is downregulated by VDR agonists in APCs and in T cells. A potentially very important activity of VDR agonists is their capacity to induce in vitro and in vivo tolerogenic DCs able to enhance CD4+CD25+ suppressor T cells that, in turn, inhibit Th1 cell responses. These mechanisms of action can explain some of the immunoregulatory properties of VDR agonists in the treatment of Th1-mediated autoimmune diseases, but may also represent a physiologic element in the VDR-mediated regulation of innate and adaptive immune responses.

Hmmm... what do I see here. Vitamin D, which the receptor in our bodies is part of the steriod receptor family. Glucocorticoides are a steroid we take for immune repression. Here it says it modulates Th1 immune responses. Again MC is associated with Th1 immune responses.

This all got me wondering about the seasonal aspect of MC. I remember it being shown more so in the summer and fall. So perhaps during the winter/spring our Vitamin D stores are depleted and so the immune response isn't regulated as well and we end up showing symptoms more in the summer/fall at least when it first starts out.

Another thing that had me wondering is why would we have an immune response that would change throughout the year? Why not keep it at a certain level all year? Perhpas the answer is the following. Think about what goes on during the winter months or at least near that time. We're all huddled up in our homes, there's less light, etc. Of course we get less vitamin D. Ok, but I still ask why? Perhaps, since we're all hudled together, inside, we're more prone to getting disease passed around. A ha! And what might fight disease more? An immune system that is more geared towards a Th1 or always on response.

What does this mean for us? Well, I'm not sure yet. Obviously we don't want our immune systems always turned off or less vigilent. And I'm not even sure that vitamin supplements get us the version of Vitamin D that is responsible for this immune suppression.

I'm starting to think that folks like Matthew and Karen have it all right to begin with. Especially with regards to supplements. Why is that? Because we're told that supplement X helps us with problem Y. What happens is we take this all year around and our bodies which are built for our environment never get a chance to work how they intended to.

For example, let's take fish oil. We've seen tons of studies showing how it helps all sorts of ailments. A big part that I'll focus on is the anti-inflamitory aspect. Well, guess what, inflamation is an important part of the processes of the body (of course ours is a lot more out of wack) and stopping inflamation stops systems from doing what they need to do, including the process of immunity and even more so with rebuilding of tissues.

Here's another example, Vitamin C. Why do we take it in large ammounts. Because of it's anti-oxident aspect. Well again, oxidation is part of the process of how the body is supposed to work. Should we not be messing with what took millions or how ever many years to develop? Should we be second guessing God? Didn't that get us into trouble to begin with? ;)

What throws a wrench into all of this is that our current bodies haven't changed much, but our environment and foods have. And by environment I mean spending more time indoors, less exercise, etc. And well all know what I mean by food. Processed, foods we weren't built to eat, same all year around, etc.

Well, the more I learn the more I realize that I (and humankind) don't know much.

Thanks,
Mike

[mle_ii]

And here's more on steroids. Let's take a look at one in particular Progesterone. It appears to have an inhibitory effect on Th1 as well, though it appears increase Th2 response (anti-body response). And in fact progesterone is increased even more during pregnancy. And why might that be? How about to protect against the "pathogen" of sperm and/or fetus? I used "pathogen" in this regard as a foreign object in the body, to which self (women) shouldn't try to fight via the immune process. If it did babies would never be born.

Is this another reason why women, particularly older women, who might produce less progesterone be more associated with autoimmune diseases?

This is a private matter I'm sure so no one need answer. :) But do any of the women here who still have periods notice a decrease in MC symptoms during their luteal phase? Probably hard to tell since it seems like some of the symptoms during a period might be the same as MC, though not to the same levels.

Mike

[mle_ii]

And from what I can tell from this article:
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum

Is that Testosterone tends to inhibit a Th1 immune response whereas estrogen + cortisol tends to increase it. Someone please correct me if I've missinterpreted.

From further articles it appears that this is the case. Testosterone inhibits immune response whereas estrogen promotes it.

Mike

[mle_ii]

Oh and so DHEA would fit in with the last bit, but not for women.

Though thinking a bit more, does this throw a wrench into the disease primarily being found in older women? Have I got something backward here or does the interplay of hormones relate?

Mike

[mle_ii]

Ok, here's another pointing towards autoimmune diseases and estrogen being linked, whereas testosterone is not.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum

[mle_ii]

Oh and so DHEA would fit in with the last bit, but not for women.

Though thinking a bit more, does this throw a wrench into the disease primarily being found in older women? Have I got something backward here or does the interplay of hormones relate?

Mike

And here's the wrench:
http://cclnprod.cc.nih.gov/dlm/testguid ... enDocument

So Postmenopausal not only do women produce less estrogen, they also produce less progesterone.