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» LymeNet Flash » Questions and Discussion » Medical Questions » Interleukin 10 Protects the Brain Microcirculation From Spirochetal Injury

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Author Topic: Interleukin 10 Protects the Brain Microcirculation From Spirochetal Injury
AliG
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J Neuropathol Exp Neurol. 2008 Sep 16.

Interleukin 10 Protects the Brain Microcirculation From Spirochetal Injury.

Londo�o D, Carvajal J, Arguelles-Grande C, Marques A, Cadavid D.

From the Department of Neurology and Neuroscience and Center for Emerging Pathogens at UMDNJ-New Jersey Medical School (DL, JC, CA-G, DC), Newark, New Jersey; and Clinical Studies Unit (AM), Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.


Spirochetal infections are an important cause of neurological disease.

In previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with Borrelia turicatae, an agent of tick-borne relapsing fever in North America, developed mild meningitis and parenchymal activation/infiltration by interleukin 10 (IL-10)-producing microglia/macrophages.

Here, we investigated the neuroprotective effects of IL-10 during spirochetal infection by comparing the outcomes of B. turicatae infection in wild-type and IL-10-deficient RAG2-deficient mice.

Mice were infected with either serotype 1 (Bt1), which causes more brain infection but lower bacteremia, or Bt2, which causes less brain infection but higher bacteremia.

Interleukin 10 deficiency resulted in early death from subarachnoid/intraparenchymal brain hemorrhage in Bt2-infected mice.

These mice had marked apoptosis of brain microvascular endothelial cells as assessed by terminal transferase-mediated DNA nick end-labeling staining.

In contrast, Bt1 infection caused milder subarachnoid hemorrhage.

Neuronal apoptosis was observed in mice infected with both serotypes and was prominent in the cerebellum.

Neutralization of tumor necrosis factor prevented death and reduced morbidity and brain injury in mice infected by both serotypes.

We conclude that IL-10 plays a critical role protecting the cerebral microcirculation from spirochetal injury possibly by inhibition effects of tumor necrosis factor.

PMID: 18800010 [PubMed - as supplied by publisher]


************************************************

How do you like THEM apples? [Wink]

--------------------
Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner.

Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006  |  IP: Logged | Report this post to a Moderator
AliG
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J Immunol. 2008 Aug 1;181(3):2076-83.

IL-10 helps control pathogen load during high-level bacteremia.


Londo�o D, Marques A, Hornung RL, Cadavid D.


Department of Neurology and Neuroscience and Center for Emerging Pathogens, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.


During relapsing fever borreliosis, a high pathogen load in the blood occurs at times of peak bacteremia.

Specific IgM Abs are responsible for spirochetal clearance so in absence of B cells there is persistent high-level bacteremia.

Previously, we showed that B cell-deficient mice persistently infected with Borrelia turicatae produce high levels of IL-10 and that exogenous IL-10 reduces bacteremia.

This suggested that IL-10 helps reduce bacteremia at times of high pathogen load by a B cell-independent mechanism, most likely involving innate immunity.

To investigate this possibility, we compared B. turicatae infection in RAG2/IL-10(-/-) and RAG2(-/-) mice.

The results showed that IL-10 deficiency resulted in significantly higher bacteremia, higher TNF levels, and early mortality.

Examination of the spleen and peripheral blood showed markedly increased apoptosis of immune cells in infected RAG2/IL-10(-/-) mice.

Neutralization of TNF reduced apoptosis of leukocytes and splenocytes, increased production of IFN-gamma by NK cells, increased phagocytosis in the spleen, decreased spirochetemia, and rescued mice from early death.

Our results indicate that at times of high pathogen load, as during peak bacteremia in relapsing fever borreliosis, IL-10 protects innate immune cells from apoptosis via inhibition of TNF resulting in improved pathogen control.


PMID: 18641346 [PubMed - indexed for MEDLINE]

--------------------
Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner.

Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006  |  IP: Logged | Report this post to a Moderator
sometimesdilly
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lordy, sultanese of sweets Ali-

you must be feeling a bit better if you can even TYPE whatever the hey that title is, much less make any sense out of it.

hope so.


[kiss] pickles

Posts: 2507 | From lost in the maze | Registered: Aug 2006  |  IP: Logged | Report this post to a Moderator
adamm
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So how do we stimulate its production?
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djf2005
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yeah,how do we?

--------------------
"Experience is not what happens to you; it is what you do with what happens to you."

[email protected]

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kgarrett
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can i get this in english [Smile]
Posts: 43 | From md | Registered: Sep 2008  |  IP: Logged | Report this post to a Moderator
Gabrielle
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quote:
Originally posted by adamm:
So how do we stimulate its production?

By taking Escherichia coli (Nissle 1917) as a regular probiotic. I didn't find a text in English that documents it - only German ones.

When I had my zytokine profile done the first time everything was normal, only my IL 10 was high. I was taking Escherichia coli at that time.

The second time I was on some kind of Acidophilus and all my zytokines were normal.

It is said that E. coli (Nissle 1917) reduces IFN-γ und IL6 (another proinflamatory Zytokine). Also, it reduces TNF and increases IL10.

Gabrielle

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TerryK
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Good post!

Testosterone may increase IL-10.

http://www.jimmunol.org/cgi/content/abstract/167/4/2060

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AliG
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quote:
Originally posted by sometimesdilly:

you must be feeling a bit better if you can even TYPE whatever the hey that title is, much less make any sense out of it.


[Big Grin] I used "cut & paste" [Wink]

What makes you think I understood it? [lol]

Right in the middle of the next thing I was posting, I spilled my entire cup of tea all over the place.

When I went back to finish posting, I saw that I had accidentally posted it (when I flung the keyboard out of the way [spinning smile] ).

I don't know if you saw THAT screwy title before I fixed it. [Roll Eyes]

I laughed my behind off, when I read your post (after that catastrophe), but was SO COMPLETELY exhausted I couldn't try to compose a reply to explain myself. [dizzy]

I have been feeling a bit better, after 6 weeks on ceftriaxone. That's about the same time I started feeling a little bit better last time, I believe.

Horizon BC/BS has been giving me grief about extensions & I'm ending up having to pay for it myself.

This inspired me to start looking for answers to prove what they are asking me for is nonsense.

I think that has sent me off on all kinds of tangents finding interesting info. Some I understand, some I don't.

I find that sometimes others comments on the studies help me to understand.

I'm not doing as good as I'd like to be because, by the time I read your reply, I had completely forgotten what this study was about.


Gabrielle-

I thought that E.coli was a harmful bacteria. [confused]


YAY TERRY!!!!! Great find!

So by screwing up our hormone production & taking down things like testosterone, they manage to take down our brain's defenses. ???


[quote]Originally posted by AliG:
Neutralization of tumor necrosis factor prevented death and reduced morbidity and brain injury in mice infected by both serotypes.
[/url]

I think I recall Marnie posting a lot of info about TNF quite some time ago. I think remember her posting about TNF-alpha.

Maybe I should go back & look for those posts.

Maybe I should get testosterone levels checked. WAIT A MINUTE!!!
I just looked. I DID have them checked & serum testosterone was fine.

I don't think I want any extra testosterone [shake] I'd better find another way. I'll have to see if Marnie had provided any thoughts on this.

Maybe I'll get lucky & she'll see this thread.

--------------------
Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner.

Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006  |  IP: Logged | Report this post to a Moderator
Gabrielle
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quote:

I thought that E.coli was a harmful bacteria. [confused]

There are pathogenic strains of Escherichia coli but there are also the good ones that everyone of us should have in his gut.

Escherichia coli strain Nissle 1917 belongs to the (very) good guys and it's in one of the best (and most expensive) probiotics here in Germany. I took it for years.

Of course, one should never take a probiotic without having made a gut flora status before. Because even the best probiotic can be bad for you if you aren't in need for this special one.

In the gut it's all about balance and if you have already lots of good Escherichia coli but you are deficient in - let's say - lactobacilli then it would be detrimental to add more E. coli because you would make the disbalance worse.

The gut flora influences the immune system (in fact it IS our immune system) and if the gut flora is not in balance then our immune system is neither.

Gabrielle

Posts: 767 | From Germany | Registered: Feb 2004  |  IP: Logged | Report this post to a Moderator
   

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