Re: Mark, others - Th2, IL-10, profound immunosuppression by borrelia

[Guest guest]

I read the first paper, and the follow-up. These are tentative,

first read responses:

1) It seems odd, and very frustrating, that we are told nothing

about the duration of disease, prior treatment history, coinfection

test results, or current clnical presentation in these patients

whose monocytes were assessed for cytokine release. Yet all patients

were from one GP's practice! How hard could it have been to compile

that data?

Without such information, we have nothing to correlate these

findings to but the selection criteria, which appear to have been

that patients were making enough Bb antibodies to test positive via

serology.

2) There is at least one study I recall clearly that shows what at a

glance seems like the inverse result. Immune cells (identified as

macrohpages, not monocytes) exposed to borrelia outer surface

proteins in that study were seen to produce high levels of IL-12,

low levels of IL-10, in a ratio extreme enough to force naive T

cells (Th0) into the Th1 phenotype. The hypothesis considered there

was that by generating this response, borrelial OSPs protected the

bugs from effective antibody development, which they stated required

the presence of Th2 cells.

3) I suppose in a very speculative way you could reconcile the

results by saying that the positive antibody status of the 'late

stage' patients acrued from the higher levels of IL-10 facilitating

Th2 cell, antibody-forming responses vs. the inflammmatory response

observed in response to borrelial OSPs in the other study I am

referring to.

4) You could end up with a forking immune response that looks a

little like this:

In response pattern 1, high levels of inflammatory cytokines are

generated but effective antibody development is minimized. Any bugs

that are killed are quickly removed from the body, but not many are.

In response pattern 2, low levels of inflammatory cytokines are

generated, but effective antibody development is increased. More

bugs are killed, but the inflammatory process needed to get the

lysed bugs and their toxins out of the body are indequate, allowing

these to accumulate.

In the first response pattern, the immune system would play a

prominent role in generating symptoms, but a minor role in directly

attacking the bugs.

In the second response pattern, the immune system would play a much

reduced role in generating symptoms, a more significant role in

attacking the bugs. The disease would actually be progressing away

from, not toward, an 'autoimmune' model (though based on the broad

reduction in cytokine release to ANY flavor of LPS, possibly toward

a model of immune deficit).

One might expect the first hypothesized pattern to correspond more

to arthralgias, the second to correspond more to central and

peripheral nervous system disease.

It's just a bunch of wild speculation on my part. What a shame that

we know nothing about the actual health status of those patients

whose monocytes were studied.

I would almost think it worth corresponding with the authors to see

if anything more can be learned.

S.

> Mark have you checked this free text out? The results are STRIKING

> but I'm still not sure I didnt see them disconfirmed somewhere

> else... this one has been on my mind a long time and I lost track

of

> the results I thought might contradict it...

>

> It says lyme patient PBMC had a 70 PERCENT reduced IFNg and TNFa

> response to LPS, compared to healthies.

>

> Doing the same comparison using borrelia lysate (which lacks LPS

but

> has other innate immune system ligands) as the stimulant found the

> same 70 percent attenuation for TNF response vs controls, but this

> time not 70 but 92 DAMN PERCENT for IFNg!

>

> Now thats what I call immunosuppression! I aint *even* lying! This

> is right from the abstract of this paper:

>

> http://www.pubmedcentral.gov/articlerender.fcgi?artid=97940

>

> This followup says IL-10 is the primary mediator of this sorry pro-

> inflammatory output:

>

> http://www.pubmedcentral.gov/articlerender.fcgi?

> tool=pubmed & pubmedid=12819085#r8

>

> If this stuff is actually correct, its like, important.

[Guest guest]

OK, found it.

The study I addressed below used whole blood, not PBMC as I said.

And it found the IFNg response to Bb 10x weaker in patients than in

controls.

THis one (also free text) used PBMC rather than whole blood, and

found the IFNg response to Bb 10x STRONGER in patients than in

controls.

Ie, the factors found are 100-fold different.

The second paper predates the first paper and is not cited by the

first paper.

Something must explain this.

> Mark have you checked this free text out? The results are STRIKING

> but I'm still not sure I didnt see them disconfirmed somewhere

> else... this one has been on my mind a long time and I lost track

of

> the results I thought might contradict it...

>

> It says lyme patient PBMC had a 70 PERCENT reduced IFNg and TNFa

> response to LPS, compared to healthies.

>

> Doing the same comparison using borrelia lysate (which lacks LPS

but

> has other innate immune system ligands) as the stimulant found the

> same 70 percent attenuation for TNF response vs controls, but this

> time not 70 but 92 DAMN PERCENT for IFNg!

>

> Now thats what I call immunosuppression! I aint *even* lying! This

> is right from the abstract of this paper:

>

> http://www.pubmedcentral.gov/articlerender.fcgi?artid=97940

>

> This followup says IL-10 is the primary mediator of this sorry pro-

> inflammatory output:

>

> http://www.pubmedcentral.gov/articlerender.fcgi?

> tool=pubmed & pubmedid=12819085#r8

>

> If this stuff is actually correct, its like, important.

[Guest guest]

could you possibly translate the jist of what this means very briefly for

those of us that

aren't literate in this stuff, if it isn't too much trouble?

BW,

Sheila

Monday, August 22, 2005, 10:09:50 PM, you wrote:

EH> Mark have you checked this free text out? The results are STRIKING

EH> but I'm still not sure I didnt see them disconfirmed somewhere

EH> else... this one has been on my mind a long time and I lost track of

EH> the results I thought might contradict it...

EH> It says lyme patient PBMC had a 70 PERCENT reduced IFNg and TNFa

EH> response to LPS, compared to healthies.

EH> Doing the same comparison using borrelia lysate (which lacks LPS but

EH> has other innate immune system ligands) as the stimulant found the

EH> same 70 percent attenuation for TNF response vs controls, but this

EH> time not 70 but 92 DAMN PERCENT for IFNg!

EH> Now thats what I call immunosuppression! I aint *even* lying! This

EH> is right from the abstract of this paper:

EH> http://www.pubmedcentral.gov/articlerender.fcgi?artid=97940

EH> This followup says IL-10 is the primary mediator of this sorry pro-

EH> inflammatory output:

EH> http://www.pubmedcentral.gov/articlerender.fcgi?

EH> tool=pubmed & pubmedid=12819085#r8

EH> If this stuff is actually correct, its like, important.

EH>

[Guest guest]

Basically, if this work is right there would probably be some

mechanism by which Bb succeeds in manipulating some hosts to get them

to make too much IL-10. IL-10 is a cytokine which is, on the whole,

antiinflammatory and suppressive of Th1 immune activity.

SInce we dont know at all where most of the borrelia are located -

I'm swinging back toward thinking they are mostly inside cells but

its just a guess - it would be impossible to specify the precise

impact of the IL-10. But, excess IL-10 could interfere with the

destruction of Bb (and other microbes) in a number of ways.

The thing is, the data are alllllllll over the map. I am surprised

these authors would publish without citing an earlier, comparable

experiment in which the results differed by 100-fold! I will probably

write to them sometime.

>

> could you possibly translate the jist of what this means very

briefly for those of us that

> aren't literate in this stuff, if it isn't too much trouble?

> BW,

> Sheila

[Guest guest]

Thanks ,

Sheila

Tuesday, August 23, 2005, 6:08:53 PM, you wrote:

EJ> Basically, if this work is right there would probably be some

EJ> mechanism by which Bb succeeds in manipulating some hosts to get them

EJ> to make too much IL-10. IL-10 is a cytokine which is, on the whole,

EJ> antiinflammatory and suppressive of Th1 immune activity.

EJ> SInce we dont know at all where most of the borrelia are located -

EJ> I'm swinging back toward thinking they are mostly inside cells but

EJ> its just a guess - it would be impossible to specify the precise

EJ> impact of the IL-10. But, excess IL-10 could interfere with the

EJ> destruction of Bb (and other microbes) in a number of ways.

EJ> The thing is, the data are alllllllll over the map. I am surprised

EJ> these authors would publish without citing an earlier, comparable

EJ> experiment in which the results differed by 100-fold! I will probably

EJ> write to them sometime.

EJ>

>>

>> could you possibly translate the jist of what this means very

EJ> briefly for those of us that

>> aren't literate in this stuff, if it isn't too much trouble?

>> BW,

>> Sheila

EJ>

[Guest guest]

Actually, sorry, Scha emailed me some observations - my reading of

that paper might have been wrong. (While reading it I kept stopping

like 10 times to re-dredge pubmed for that contrary finding!)

Specifically, the fact that removing IL-10 (by neutralizing it with

antibodies) " fixed " the weak reaction of lyme blood to borrelia, does

not prove that IL-10 caused the weak reaction. Possibly they implied

so, or possibly I sorta made it up. I'm too tired to look right now!

<james@c...> wrote:

>

> Thanks ,

> Sheila

[Guest guest]

I have severe Igg subclass dysfunction since I have had lyme and

wonder if the benicar would correct this. Any data anywhere where I

can search?

thank you, Donna

> >>

> >> could you possibly translate the jist of what this means

very

> EJ> briefly for those of us that

> >> aren't literate in this stuff, if it isn't too much trouble?

> >> BW,

> >> Sheila

>

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> EJ>