Author Topic: T REG cells  (Read 580 times)

b_jim

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T REG cells
« on: May 18, 2019, 03:07:29 PM »
I continue my search about a *possible* negative role of tryptophane is Pois....

Tryptophan can be converted  to Niacine (=vitamine B3).
Tryptophan can be converted to Kynurenine.

 L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin.

Kynurenine is involved in the auto-immune answer by release of Reegulatory T Cells (=T REG cells).


I wonder if the niacine therapy works with this. When a poiser take  a strong dose of niacine, it blocks the conversion of tryptophane to niacine and avoid the synthesis of kynurenine and TREG.

For sugar, it's easy to understand high sugar in blood will increase tryptophan absorbtion.




« Last Edit: May 18, 2019, 03:17:58 PM by b_jim »
Taurine = Anti-Pois

Nas

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Re: T REG cells
« Reply #1 on: May 18, 2019, 05:26:57 PM »
Kynurenine is involved in the auto-immune answer by release of Reegulatory T Cells (=T REG cells).
Do you have a source for that?

Btw I take L-Tryptophan supplement and it helps a little with sleep and OCD.

b_jim

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Re: T REG cells
« Reply #2 on: May 22, 2019, 02:07:12 PM »
You can find some scientific or non-scientific articles about this.
But, I want to test again tryptophan (pumpkin seed) + sugar boost 30 min before orgasm.
Last time the effect was extremely clear.

The balance of serotonin is very complex. Too low leads to depression symptoms. But too high seems leads to anxiety !
« Last Edit: May 22, 2019, 03:26:22 PM by b_jim »
Taurine = Anti-Pois

demografx

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Re: T REG cells
« Reply #3 on: May 22, 2019, 04:27:49 PM »
Thanks, b_jim, tryptophan might have a more natural serotonin effect than SSRI’s, which I’ve been taking for years.
10 years of major POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks associated with it.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business.

b_jim

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Re: T REG cells
« Reply #4 on: June 09, 2019, 10:38:57 AM »
I've make the test again... and it didn't work...
I don't understand why...
If not tryptophane, is inflammation the culprit ?

We should contact Dr House  :P
Taurine = Anti-Pois

Nas

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Re: T REG cells
« Reply #5 on: June 09, 2019, 01:02:43 PM »
I've make the test again... and it didn't work...
I don't understand why...
If not tryptophane, is inflammation the culprit ?

We should contact Dr House  :P
So it's neither Tryptophan nor inflammation for my case.
I'm looking to try memantine for exitotoxicity theory.
And a dopamine antagonist to see if POIS might involve excess arousal.

b_jim

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Re: T REG cells
« Reply #6 on: June 10, 2019, 06:04:57 AM »
Maybe you are right. Maybe NMDA receptor is the key of all this.
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Nas

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Re: T REG cells
« Reply #7 on: June 10, 2019, 07:03:48 AM »
Maybe you are right. Maybe NMDA receptor is the key of all this.
Well I have very nice record of never being right on POIS, so. We'll see.

b_jim

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Re: T REG cells
« Reply #8 on: June 16, 2019, 12:00:26 PM »
I made the test again and it din't work.
I made 2 meals with carbohydrates (junk food) + 100g of seeds and it didn't make the symptoms worse. I tought digestive Leukocytosis could be linked too and white cells could be involved, I was wrong :/
Taurine = Anti-Pois

Muon

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Re: T REG cells
« Reply #9 on: July 04, 2019, 07:30:58 AM »
Interesting b_jim, I was totally unaware that the tryptophan-IDO-Kynurenine metabolism pathway affected the Treg/Th17 axis.

An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells.

This could link neurotransmitters to the regulation of immune tolerance. Kynurenine can differentiate T cells into FOXP3+ Tregs which play a role in the development of (auto)-immune diseases. Now you may ask yourself the question what happens when kynurenine is chronically low?

FOXP3+ expressed Tregs should be investigated, I'm not surprised when it's showing low levels.

You can test these cells in Berlin but only the total Treg pool, they probably don't look at Treg subsets. It costs around 50 euro:
https://www.imd-berlin.de/fileadmin/user_upload/Anforderungsscheine/SI_Anforderung_IGEL.pdf (number 9 on this list)
You can print this list, put a cross at the parameter you want to test, just walk into the department and they will test it for you without intervention of any doctor or insurance company.

For other parameters you can use the lower search bar on this page: https://www.imd-berlin.de/nc/leistungsverzeichnis.html
« Last Edit: July 04, 2019, 08:31:48 AM by Muon »

nanna1

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Re: T REG cells
« Reply #10 on: September 10, 2019, 11:57:24 PM »
Interesting b_jim, I was totally unaware that the tryptophan-IDO-Kynurenine metabolism pathway affected the Treg/Th17 axis.

An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells.
  Interesting! When kynurenine activates the aryl-hydrocarbon receptor (AhR), it causes immunosuppression of the innate immune system. The aryl hydrocarbon receptor activation leads to a downregulation of il-2, il-17 and upregulation of il-22, il-10 (Ref1, Ref2, Ref3). This causes a decrease in NK cells (Ref), TH-17, neutrophil and macrophages. But it increases T reg and dendritic cells which leads to immune-tolerance (reduced immunity) to pathogens. If orgasm/ejaculation triggers something the induces IDO, this could explain some of the POISer medical data for white blood cells and cytokines as well as symptoms related to the gut that some experience.

It should be noted that kynurenine suppresses autoimmunity and establishes immune tolerance through AhR (Tryptophan degradation in autoimmune diseases). So IDO and the kynurenine pathway decrease and prevents autoimmune diseases.
"Tryptophan metabolism activated by indoleamine 2,3-dioxygenase 1 (IDO1) but not arginine metabolism is often associated with protective effects in autoimmune disorders and reduction of autoantibodies to therapeutic proteins." - Amino acid metabolism as drug target in autoimmune diseases (2019)
 
  Salicylamide is an over-the-counter (OTC) aryl-hydrocarbon receptor (AhR) inhibitor (Ref). Kaempferol also inhibits AhR (for potential hypothesis testing) (Ref). (Kynurenine has a half-life of 20mins in the blood).

This receptor is also stimulated by some types of food (diet):
"The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is activated by small molecules provided by the diet, microorganisms, metabolism, and pollutants. AhR is expressed by a number of immune cells, and thus AhR signaling provides a molecular pathway that integrates the effects of the environment and metabolism on the immune response....Although AhR was initially recognized as the mediator of the toxic effects of dioxins, multiple physiologic ligands are provided by the diet, the commensal flora, and also the host metabolism." -Regulation of the Immune Response by the Aryl Hydrocarbon Receptor
Figure from: Tryptophan Catabolites from Microbiota Engage Aryl Hydrocarbon Receptor and Balance Mucosal Reactivity via Interleukin-22

Figure from: The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells

  AhR is an important factor in IBD/IBS (see Figure 4 of "Aryl hydrocarbon receptor and intestinal immunity (2018)")

  This is a very promising lead to knowing the cause of POIS!
« Last Edit: September 11, 2019, 09:06:16 AM by nanna1 »
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

Muon

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Re: T REG cells
« Reply #11 on: September 12, 2019, 12:04:16 PM »
Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides like in the article above

And could IBD lead to POIS in the following way?: What if chronic colonic irritation induces sensitization of afferent nerves to neuropeptides in other parts of the urogenital system?

Could neuropeptides from seminal fluid induce afferent nerve firing in the urinary tract? These nerves run all the way up to the brain. The urogenital afferent nerve firing makes the brain signaling back via efferent nerves to unrelated locations.

Efferent nerves could release neuropeptides on their turn at these locations (like close to the skin, this could explain burning sensation of lower arm surface for instance). These released neuropeptides could couple back again to afferent nerves at the same location. This leading to a positive feedback loop, basically a perpetual motion.

https://en.wikipedia.org/wiki/Afferent_nerve_fiber

From my own experience, precum can lead to burning sensations of the the penile urinary tract. I also had problems with a burning sensation of my lower arms in the past. Could these effects both be explained by afferent/efferent nerve firing/release by/of neuropeptides.

I see that the genetic factors you have posted in your last picture can be tested as well:
https://www.imd-berlin.de/fileadmin/user_upload/Anforderungsscheine/SI_Anforderung_IGEL.pdf
Hmm I didn't know they were part of Chron's disease. Vandemolen's brothers both got Chron's disease and that disease is Th1 mediated as well if I'm not mistaken.

This could also tie into the threads of members who complain about IBS/IBD related symptoms like member going less crazy who mentioned relieve/disappearance of POIS symptoms when avoiding food triggers.

My grandma felt better btw when she did not eat and also had problems with cabbage. My brother gets cognitive dysfunction from food.

The difference between primary and secondary poisers might be that the primary ones have an additional genetic mutation leading to intestinal problems.

My brother tested serum serotonin again at his local hospital and the result is still low. This could mean that these serum neurotransmitter values are chronically low. Since the majority of serum levels are stemming from the gut, these values might actually be very valuable in this theory. It could reflect intestinal inflammation. His IL-17 is also decreased.

The cytokokines that are changing in my case are decreasing after orgasm and shoot right back up like IL-10:
https://poiscenter.com/forums/index.php?topic=2891.0
It seems to be dipping at a certain time frame. IL-17, IFN-g and Il-2 also decreases somewhat and shoot back up. I wonder what happens if I measure these neurotransmitter serum levels (serotonin,tryptophan, kynurenine, IDO activity) at a similar time frame. Also Th1 polarization could indicate intestinal problems.

I'm not sure intestinal Treg infiltration affects peripheral values of pTregs. I need to read more of what you have posted nanna about these pathways related to the intestinal tract.

nanna1

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Re: T REG cells
« Reply #12 on: September 14, 2019, 02:13:10 PM »
Hi Muon,

  You have some interesting ideas. And it helps that you also have data and case reports from family. I know that you are probably familiar with some of the things I will say in this post, but since some of these topics are highly technical, I will try to over-explain what I am trying to say so that others can follow the discussion.
...What if chronic colonic irritation induces sensitization of afferent nerves to neuropeptides in other parts of the urogenital system?
  This might imply that POIS requires (or is caused by) IBS. I think to make this conclusion, we would have to rule out the possibility that the THING that causes IBS does not also independently cause POIS. In other words distinguish between correlation and causation.

Could neuropeptides from seminal fluid induce afferent nerve firing in the urinary tract?...
  In the recent paper by Alex Strashny, it implies that there are people who only experience POIS from masturbation but not sex and/or nocturnal emission (NE) ("First assessment of the validity of the only diagnostic criteria for postorgasmic illness syndrome" (Alex Strashny, 2019)). There are other published papers showing POISers that do not experience POIS durning sex even though they ejaculate (see "Benign coital headache relieved by partner's pregnancies with implications for future treatment" (Selwyn Dexter, 2009)). On this forum also, there are some who self-report that POIS happens more often after masturbation than from sex and NE. Assuming that the neuropeptides in semen do not depend on whether a person has sex, masturbates or has nocturnal emissions, how could these neuropeptides cause POIS in one form of ejaculation and not the other two?

These nerves run all the way up to the brain. The urogenital afferent nerve firing makes the brain signaling back via efferent nerves to unrelated locations...Efferent nerves could release neuropeptides on their turn at these locations
  You actually don't need brain-feedback to cause sensation in an unrelated location. There is a phenomenon call refered pain. An afferent signal in one place can cause an effernent signal in another unrelated location directly. Refered pain is a phenomenon that is used in ancient medical techniques such as trigger points techniques and acupuncture. Percutaneous Tibial Nerve Stimulation (PTNS) also works on the same principle.

  With that said, note that the afferent/efferent signals pass through the ganglia neurons of the spinal cord. Ganglia are like "internet routers" for the body. They route signals to-and-from different parts of the body, but also they route signals to-and-from the brain. The brain cannot tell the difference between a signals coming from the spinal ganglion and signals from afferent/efferent communication.
  If an S ganglia (at the bottom of the spinal cord) misfires, it can send a signal to the brain that the urogenital track is burning or iching or being touched or feeling pain or pleasure (see below figure: S2, S3, S4). Those feelings can feel real as if there is something happening in the genitals when in fact there is nothing happening to the genitals. Even if there is no inflammation in the genitals, an injured ganglia neuron can make it feel like there is inflammation in the genital location. The same is true for every other organ of the body. All signals to the brain pass through (and are controlled by) the spinal cord ganglion.
S2, S3, S4
  If a person has a limb amputated for some reason, they can often still "feel" their missing limb because the spinal ganglia neurons were not removed and are still sending signals to the brain. This is called phantom limb. Interestingly Dr. Stuart Meloy figured out how to give women orgasms using surgically implanted electrically stimulation of the S2 ganglion (Dr. Stuart Meloy bio).

 
  Below is a complete map of the C, T, L, and S series ganglion locations (left spinal cord image) and the locations of the body that they influence (right image: sliced front-back).

From my own experience, precum can lead to burning sensations of the the penile urinary tract. I also had problems with a burning sensation of my lower arms in the past. Could these effects both be explained by afferent/efferent nerve firing/release by/of neuropeptides.
  How do you rule out norepinephrine (noradrenaline) causing both the release of preejaculate and the burning sensation simultaneously. The some of the adrenergic receptors contract smooth muscle such as in the bladder, seminal vestigal and prostate. This causes pressure to urinate, ejaculate, etc... A norepinephrine release could potentially also cause the burning sensation that you feel. There is still no published paper showing that POISers are sensitive/hypersensitive to semen. 22 percent of Dr. Waldinger's POISers did not have positive skin prick test. However, there are three published POIS case-studies showing that POISers are not sensitive to semen.

  So far, the most successful treatments for POIS in the published literature are diclofenac (80 percent relief, Goldmeier (2010)) and norethisterone (95 percent relief, Dexter (2009)). Both of these treatments produced (same-day) results, were tracked for several months and remained effective throughout (see POIS literature review). Both papers suggest POIS triggers not involving semen.

...going less crazy who mentioned relieve/disappearance of POIS symptoms when avoiding food triggers... My grandma felt better btw when she did not eat and also had problems with cabbage. My brother gets cognitive dysfunction from food...My brother tested serum serotonin again...and the result is still low...His IL-17 is also decreased.
  I recommend taking a look at the ligand table for the aryl hydrocarbon receptor (AhR). The Indole Metabolites (at the top) are found in cabbage. AhR also inhibits the release of il-17 and il-2.

The difference between primary and secondary poisers might be that the primary ones have an additional genetic mutation leading to intestinal problems.
  If you look through the raw data from the last POIS survey (Alex Strashny, La_pet1te_mort) there is no clear age range for when POIS starts. For most genetic disease that I am aware of, there is an age range where the symptoms of the disease start to manifest. But POISers seem to acquire POIS at any stage in life. This makes me skeptical of any strong genetic factor for POIS. But maybe there are weak genetic propensities for POIS.

The cytokokines that are changing in my case are decreasing after orgasm and shoot right back up like IL-10:
https://poiscenter.com/forums/index.php?topic=2891.0
...IL-17, IFN-g and Il-2 also decreases somewhat and shoot back up. I wonder what happens if I measure these neurotransmitter serum levels (serotonin,tryptophan, kynurenine, IDO activity) at a similar time frame...
  In Effects of Sexual Arousal on Lymphocyte Subset Circulation and Cytokine Production in Man (P Haake, U Hartmann, et al., 2004), they showed that in normal people Helper T cells (CD3+CD4+), Suppressor T cells (CD3+CD8+), B cells (CD3-CD20+), IL-6 and TNF-alpha do not change during sex/orgasm. However, they also showed that natural killer cells (NK cells) and other Leukocytes from the innate immune system do increase during sex/orgasm in normal people. It would be really cool if we could reproduce this experiment (measuring all the same parameters) in POISers. We could use the results of the P Haake, U Hartmann, et al. study as a healthy control. This way we know if there is a difference between POISers and non-POISers.
  Kruger, et al. showed that serotonin is released during sex/orgasm. So measuring serotonin, tryptophan, kynurenine would be interesting. As long as you have these, you don't need to measure IDO directly. But I also think that measuring AhR activity (before, 5min after, 1 hour after) will be important for future POIS research since:
--tryptophan and arachidonic acid metabolites stimulate this receptor
--it affects IBD/IBS
--it affects autoimmunity
--it suppresses the innate immune system

  Thanks for sharing your insightful ideas. Let me know what you think about this.
« Last Edit: September 14, 2019, 04:52:38 PM by nanna1 »
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

Hopeoneday

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Re: T REG cells
« Reply #13 on: September 14, 2019, 03:04:38 PM »
We should contact Dr House  :P

It will be my plesure to help, yust ask  8)

Muon , Nana... intresting discusion , IBD connection...
its seams that in some poisers O induce IBD , not oposite.
« Last Edit: September 14, 2019, 03:09:34 PM by Hopeoneday »
Dr-pois.

Nas

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Re: T REG cells
« Reply #14 on: September 14, 2019, 04:28:38 PM »
How the hell does someone with so much knowledge not figure out POIS already!!! Jeez Nanna.

Honestly harking back to the discussion, I highly think POIS is a neurological event that causes phantom immune behaviors.

Quote
  Kruger, et al. showed that serotonin is released during sex/orgasm. So measuring serotonin, tryptophan, kynurenine would be interesting. As long as you have these, you don't need to measure IDO directly. But I also think that measuring AhR activity (before, 5min after, 1 hour after) will be important for future POIS research since:

I heard about this, yet I clearly suffer from low serotonin symptoms such as pure OCD, depression and anxiety.