Lipopolysaccharide / LPS Demyelination / Apoptosis

[notasperfectasyou]

There is some on TIMS about LPS, but it doesn't have it's own thread. When I read these two articles I wondered, "Has any one else at TIMS read these?"

Dr. Felts et al. 2005 Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide

Dr. Bannerman et al. 2003 Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis

1) What do you think?
2) Do you know of other related research on this? Other articles?
3) Is there anything anyone can get at the supplement store that clears LPS out of the body?

Ken

[peekaboo]

notasperfectasyou -

Yes I agree this is very pertinant to our cause. especially on the viral / bacterial level. googling lipopolysaccharide returns many hits. I found this one and it seems to fit the flow of TIMS


Abstract: Proinflammatory cytokines mediate the toxic effects of superantigenic staphylococcal exotoxins (SE) and bacterial lipopolysaccharide (LPS). Triptolide, an oxygenated diterpene derived from a traditional Chinese medicinal herb, Tripterygium wilfordii, inhibited SE-stimulated T-cell proliferation (by 98%) and expression of interleukin 1beta, interleukin 6, tumor necrosis factor, gamma interferon, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta by human peripheral blood mononuclear cells (PBMC). It also blocked the production of these cytokines and chemokines by LPS-stimulated PBMC in a dose-dependent manner. These results suggest that triptolide has potent immunosuppressive effects even counteracting the effects of superantigens and LPS. It also may be therapeutically useful for mitigating the pathogenic effects of these microbial products by downregulating the signaling pathways activated by both bacterial exotoxins and endotoxins.

http://www.stormingmedia.us/96/9648/A964844.html

now what is triptolide? Googling I will go

[peekaboo]

Found something

http://www.paypaytech.com/products/Trip ... agodYF-nuw


Its a start any way....Holly

[notasperfectasyou]

I did a quick scan of the net and found a few articles about triptolide. Do you take it? Inhibits NF-Kb, IL-2, HSP, IL-6, G-CSF, ICAM-1. WoW! I need to read more about this, but I also need to keep this thread focused on LPS. I'll look at Triptolide later.

Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f.

More on LPS? Anyone?

[Shayk]

Ken

Here's something about steroids inhibiting LPS induced NO, etc.--not sure it's exactly relevant.

Inhibition of LPS-induced iNOS and NOS induced synthesis in primary rat microglial cells

As a model system, we used primary rat microglial cells which produce NO synthase and subsequently release NO upon stimulation with lipopolysaccharide (LPS). Among the substances tested, the glucocorticoids prednisone, hydrocortisone, dexamethasone and progesterone as well as transforming growth factor-beta (TGF-beta) dose-dependently inhibited LPS-induced nitric oxide synthase (iNOS) and NO synthesis.

Progesterone is available over the counter and also helps remyelinate, even old rats. Before trying it I'd think Kim would want to have her progesterone level tested though.

And, you may have seen this one about DHEA somewhere in the archives of TIMS. But, if not....

Dehydroepiandrosterone inhibits lipopolysaccharide-induced nitric oxide production in BV-2 microglia

The results showed that DHEA but not DHEAS significantly inhibited the production of nitrite in the LPS-stimulated BV-2 cell cultures. Pretreatment of BV-2 cells with DHEA reduced the LPS-induced iNOS mRNA and protein levels in a dose-dependent manner.

Again, important to have one's DHEA level tested before trying it. There really are lots of reasons (IMHO) why healthy hormone levels could be a plus in MS.


Sharon

[LR1234]

Thats something that always confuses me....They talk about the benefits of oestrogen during pregnancy which is why they are trialing it but I thought progesterone levels are much higher in pregnancy so why are they not studying that more??

Can anything counteract LPS induced NO?

[peekaboo]

the sex hormones are dangerous to mess around with. They have been atributed to certain cancers ie: breast, cervics even for men too but forget which.

I was on a bio-indentical hormone regimen. I was first saliva tested for estrogen progesterone and testosterone. Also my thyroid levels too (blood spot test) as well as cortisol levels. I am menopausal so the test showed an imbalance of all these for my age etc. and was given a rx for bio-identical estrogen and progesterone. Also rx Arend-Al for adrenal support (cortisol reducing).

Bio-indentical hormones match the exact chemical formula as our bodies. re pharma estrogen is made from pregnant house pee! and is not an exact match to human estrogen.

I had to quit because of $$$ it is not cheap. I still use Adren-All to combat that nasty cortisol (pill form) which can be bought even through amazon still not cheap.

Hope this helps

[notasperfectasyou]

Here's the rub - at least for today, This Lipopolysaccharide stuff is residue from certain kinds of bacteria getting wiped out in your body. So, it's not exactly an uncommon event. But, if we wonder at times, "Gee, what are some of the things that might breakdown the Blood Brain Barrier?" Well, this is one of them:

Friedman et al. 1997 Lipopolysaccharide Induces Disseminated Endothelial Apoptosis Requiring Ceramide Generation

Interesting that you'd need an immune system around to be killing the bacteria in order to generate the LPS? Ken

Cheerleader!?!?!?!?!?!

[cheerleader]

Hey Ken-
Very interesting research. Makes sense that LPS would activate the endothelium, but the aptosis is curious.

We conclude that the intraspinal injection of LPS results in inflammation and subsequently in prominent demyelination. The mech- anisms underlying the demyelination are not clear, but it is notable that it typically begins with disruption of the adaxonal myelin. Indeed, there is an early loss of myelin-associated glycoprotein within the lesion, despite the persistence of proteolipid protein. This combination is a feature of the pattern III lesion recently described in multiple sclerosis (Lucchinetti et al., 2000), and we therefore suggest that LPS-induced demyelination may serve as the first experimental model available for the study of this type of multiple sclerosis lesion.

The researcher state that this type of lesion loks like Lucchinetti's #III, which is:
Pattern III
-Distal oligodendrogliopathy, diffuse lesions with variable inflammation and pronounced microglial activations
-Indistinct border
-not centered around venule
-striking loss of myelin associated glycoprotein
-no compliment activation
-Pattern associated with hypoxia
-dying back of oligodendrocyte
-Looks like white matter stroke
-Represents the early stage of lesions during an exacerbation
-Defects in mitochondrial respitory chain

This is severe NO disruption...looks like hypoxia and stroke.
I need to read more, and have to make dinner for my boys!
I promise I'll get back with more thoughts. There's alot to digest. In the research, not my dinner
cheer

[cheerleader]

Quickie search while cooking...
looks like alpha-lipoic acid to the rescue again!
http://circres.ahajournals.org/cgi/cont ... l/97/9/880

Our in vivo data also demonstrated that LA decreased LPS-induced fractalkine expression in arterial endothelial cells, endocardium, and villous endothelium. Therefore, LA warrants further evaluation as an antiinflammatory drug in endotoxemia. Because current therapy for patients with sepsis is still unsatisfactory, there have been continued efforts to find new and effective means to improve outcome by modulating inflammatory responses. Our results indicate that LA may be promising as an adjunctive treatment for endotoxemia, although the results presented here need further evaluation with other clinically relevant animal models.

AC