Author Topic: Information about Cytokines and other biological substances  (Read 3400 times)

Quantum

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Information about Cytokines and other biological substances
« on: August 28, 2016, 10:49:38 AM »
For those wondering about what cytokines, following is an explanation I hope is easy to understand.  I know this post is longer than what most POISers attention span can accept, if you have brain fog as a major symptom and you are currently in POIS, but I think it will be helpful in understanding what researchers are talking about in POIS papers.  I think that Dr Waldinger may refer to cytokines as part of the cause of POIS symptoms, in his future work, so this will help you understand what he is writing about.  I also had written here about the role I think cytokines have in some POIS symptoms clusters, but I think I never took the time to really explain what they are, so I thought it would be a great time to do it, considering the latest review article of Dr Waldinger  ( for the link to the article, see http://poiscenter.com/forums/index.php?topic=2346.0 )

You can think of cytokines as "micro-hormones", like small hormones produced at the cells level.  These micro-hormones are produced by a limited number of cells at a time,  in a specific region of the body, like mast cells of the prostate region, for example ( POIS-related example!).  The effect of cytokines are usually short range or limited in range, meaning they will not affect the whole body, but some specific cells, usually not so far away, and not every cells of the body.  In contrast, hormones are produced by a massive amount of cells grouped in a gland, and they often have long-reaching effects, and may even affect every cells in the body ( like thyroid hormones, or insulin, which is produced by the pancreas, and affect all cells in the body ).  But there is no definite frontier between hormones and cytokines in current medical science, there are gray zones and exceptions.   So, some cytokines can act as immune messengers that have profound effects on the whole body... which is what Dr Waldinger is proposing as part of POIS pathophysiology, now.  Cytokines like interleukin-1 (IL-1), interleukin-6,  or TNF-alpha ( Tumor Necrosis Factor alpha) , and many others, are powerful and have effects on the whole body even if produced in small amount.  Part of this power is due to the "domino effect" that can be seen in the immune system.  For example, mastocytes cells ( mast cells, a kind of white blood cells that act as immune "sentinel") can release cytokines following a reaction in a small part of the body ( for example, like maybe the case in POIS, in the prostate region), and this reaction will spread from one region of the body to another, activating other cytokines and other hormones, spreading like a wave, and also spreading through the blood stream, which will transport those cytokines/immune messengers away, like into the brain.

This rather slow progression of the cytokines "domino effect" from one group of cell to the next may explain the delay seen for POIS symptoms to be fully activated ( the survey done by the Rutgers team with members here show a mean delay of 2 to 3 hours after ejaculation before the full POIS attack has developed).  This fits exactly with a "delayed hypersensitivity reaction", the type IV hypersensitivity reactions, a term Dr Waldinger was already using as a hypothesis for POIS in his 2011 article ( part 1).  He said at the time that POIS seems to imply both a Type I ( immediate) and a Type IV ( delayed) hypersensitivity reaction.

It is important to note that once this spreading wave of inflammation reach the liver, a major event occurs:  the liver, in reaction, produce the powerful "acute phase proteins", another type of immune messenger, including the well-known C-Reactive protein ( CRP), that will further intensify the whole body reaction ( fever, flu-like symptoms, etc).  This can be detected in blood tests, directly ( CRP levels), or indirectly  ( ESR, erythrocytes sedimentation rate).  I mention that because it could happen that CRP and ESR blood test results could be talked about in Dr Waldinger future papers as well.  They are usually high in auto-immuen diseases, so I wouldn't be surprised if he would measure them in POIS subjects during POIS attack.

The faster spreading of some symptoms, like brain fog seconds after O for some members, could be explained by a fast delivery of some specific cytokines through the blood stream to the brain  ( like a morphine injection will reach the brain quite fast through the blood stream), or by a type I, immediate hypersensitivity reaction ( but that may be the same thing than fast delivery through the blood stream !).   These immediate brain symptoms could also be caused by the neurotransmitters released in the brain at the time of orgasm, but that is a neurologic cause, and that would imply that POIS could be a combination of 3 types of different causes:  immediate immune effects, immediate neurologic effects, and delayed immune effects.  It is still too soon to discern which are really present in POIS or not.

Do not hesitate to ask questions about cytokines or the immune system, and I will do my best to come up with a valid and easy to understand answer.



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b_jim

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Re: Information about Cytokines and other biological substances
« Reply #1 on: September 11, 2016, 12:00:29 PM »
The problem is we have no CRP positive test to prove this theory. It's a very sensitive parameter and th blood test may show something during hours after ejaculation.
Taurine = Anti-Pois

Jimmy

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Re: Information about Cytokines and other biological substances
« Reply #2 on: September 11, 2016, 12:29:52 PM »
Thank you very much Quantum for your effort on this subject.

Your way in explaining things is awesome !


Quantum

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Re: Information about Cytokines and other biological substances
« Reply #3 on: September 11, 2016, 09:30:48 PM »
The problem is we have no CRP positive test to prove this theory. It's a very sensitive parameter and th blood test may show something during hours after ejaculation.

Hi b_jim,

I do hope that Dr Waldinger will do measure CRP in his new study.  He has expressed the intention to find biomarkers for POIS, so this is a good candidate, but not the only one.   Maybe they also did some blood tests in the Rutgers study, I don't know.  But it would be great too.
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Quantum

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Re: Information about Cytokines and other biological substances
« Reply #4 on: September 11, 2016, 09:32:45 PM »
Thank you very much Quantum for your effort on this subject.

Your way in explaining things is awesome !


Thank you for your very supportive and positive comment, Jimmy, I appreciate it !  :)
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demografx

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Re: Information about Cytokines and other biological substances
« Reply #5 on: September 12, 2016, 01:16:56 PM »
Thank you very much Quantum for your effort on this subject.

Your way in explaining things is awesome !

       :)
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: Information about Cytokines and other biological substances
« Reply #6 on: September 12, 2016, 02:42:15 PM »
The problem is we have no CRP positive test to prove this theory. It's a very sensitive parameter and th blood test may show something during hours after ejaculation.

Hi b_jim,

I do hope that Dr Waldinger will do measure CRP in his new study.  He has expressed the intention to find biomarkers for POIS, so this is a good candidate, but not the only one.   Maybe they also did some blood tests in the Rutgers study, I don't know.  But it would be great too.

I hope too. But it's difficult to think he didn't do it in tth first studies. I'm not convinced by immune system theory but in the contrary case, CRP would be the first thing I've tested.
Taurine = Anti-Pois

Nas

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Re: Information about Cytokines and other biological substances
« Reply #7 on: February 20, 2019, 04:49:53 PM »
Thanks for certainlypois for guiding to this post. This will be great to discuss Cytokines.
I have fully read what Quantum mentioned. Unfortunately it still leaves much to be asked. I feel like I can rule out brain inflammation, at least personally, as the cause of these symptoms. I can also rule out Catecholamines depletion. I don't know where to go from here. But I've read somewhere that certain Cytokines can effect certain metabolic functions like the tryptophan pathways and the kynurenine pathway. I don't know much about this metabolic cycle, so if anyone has knowledge please say.

Nas

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Re: Information about Cytokines and other biological substances
« Reply #8 on: February 20, 2019, 06:51:16 PM »
I think I found it: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141874/

It says:
"Data indicate that cytokines and their signaling pathways including p38 mitogen activated protein kinase have significant effects on the metabolism of multiple neurotransmitters such as serotonin, dopamine and glutamate through impact on their synthesis, release and reuptake. Cytokines also activate the kynurenine pathway which not only depletes tryptophan, the primary amino acid precursor of serotonin, but also generates neuroactive metabolites that can significantly influence the regulation of dopamine and glutamate."

I'm a bit confused though, and this is where my medical knowledge fails me. Can cognitive symptoms in POIS be caused by down-regulation of glutamate? Is the activation of the kynurenine pathway responsible of this down-regulation?
« Last Edit: February 20, 2019, 07:47:13 PM by Nas »

Quantum

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Re: Information about Cytokines and other biological substances
« Reply #9 on: February 20, 2019, 09:47:02 PM »
Thanks for certainlypois for guiding to this post. This will be great to discuss Cytokines.
I have fully read what Quantum mentioned. Unfortunately it still leaves much to be asked. I feel like I can rule out brain inflammation, at least personally, as the cause of these symptoms. I can also rule out Catecholamines depletion. I don't know where to go from here. But I've read somewhere that certain Cytokines can effect certain metabolic functions like the tryptophan pathways and the kynurenine pathway. I don't know much about this metabolic cycle, so if anyone has knowledge please say.


Hi Nas,

About the tryptophan pathway, and the kynurenine pathway, and their possible role in POIS, you an see some explanation in this thread:

http://poiscenter.com/forums/index.php?topic=1988.msg15559#msg15559 

I also recommend you study this diagram carefully ( it is presented in the thread just above):

http://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory 


You can also read here, about the kynurenine pathway, and the role of IDO and TDO in my hypothesis ( put in perspective in an overall hypothesis on POIS physiopathology I described some years ago):  http://poiscenter.com/forums/index.php?topic=2078.msg16431#msg16431   


If you dig about the kynurenine pathways and tryptophan pathway, you will find why I have developed interest for natural TDO inhibitors, and IDO inhibitors, and are using them.


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Nas

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Re: Information about Cytokines and other biological substances
« Reply #10 on: February 21, 2019, 01:27:36 AM »
Thanks Quantum, I've read it quite well, though I never really understood why kynurenic acid causes brain fog? Is it because of the depletion of tryptophan?

b_jim

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Re: Information about Cytokines and other biological substances
« Reply #11 on: February 21, 2019, 01:46:12 PM »
Yes. More and more doctors think depression is mainly a problem of inflamation by this pathway .
You made a very good job.
But we know that semen is rich on serotonin, melatonin and tyrotropin releasing hormone enough to affect positively women (an negatively men?)
Taurine = Anti-Pois

Quantum

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Re: Information about Cytokines and other biological substances
« Reply #12 on: February 22, 2019, 07:07:47 AM »
Thanks Quantum, I've read it quite well, though I never really understood why kynurenic acid causes brain fog? Is it because of the depletion of tryptophan?

Hi Nas,

In addition to what B_jim said about taking away tryptophan form serotonin synthesis, kynurenic acid becomes toxic on its own when too hign level in the brain , see https://en.wikipedia.org/wiki/Kynurenic_acid#Role_in_disease  ( encephalitis-like symptoms, confusion, etc...)

Kynurenic acid, by acting as a powerful NMDAr inhibitor, slows down the brain, so my hypothesis is that it it responsible for cognitive impairments in POIS ( slow thinking, cognitive issues, speech impairment, problem solving capacities decreased,...).   I do not have these symtpoms, but lots of emotional symptoms, that, in my hypothesis, are linked to quinolinic acid, another branch in the kynurenins pathways.  For most POISers, it seems that they get symptoms from both of these branches, kynurenic acid and quinolinic acid production.

« Last Edit: February 22, 2019, 07:15:22 AM by Quantum »
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Nas

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Re: Information about Cytokines and other biological substances
« Reply #13 on: February 22, 2019, 11:23:48 AM »
Quantum,
So it says it blocks glycine site NMDA receptors, so it decreases glutamate neurotransmission. But I don't understand its connection with schizophrenia; it says that it increases dopamine fire rate in midbrain, yet I can swear that POIS is more of a decrease in dopamine function. Until now no POISer reported POIS caused psychosis.
On the other hand what are the therapeutic options in this case? NMDAr agonists? Increase glutamate production? Supplementing for lost tryptophan?
« Last Edit: February 22, 2019, 12:19:40 PM by Nas »

Quantum

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Re: Information about Cytokines and other biological substances
« Reply #14 on: February 23, 2019, 11:40:18 AM »
Quantum,
So it says it blocks glycine site NMDA receptors, so it decreases glutamate neurotransmission. But I don't understand its connection with schizophrenia; it says that it increases dopamine fire rate in midbrain, yet I can swear that POIS is more of a decrease in dopamine function. Until now no POISer reported POIS caused psychosis.
On the other hand what are the therapeutic options in this case? NMDAr agonists? Increase glutamate production? Supplementing for lost tryptophan?

Hi Nas,

what interest me more in the effect of kynurenic acid is the confusion and encephalite-like symptoms, showing that POIS could be a temporary, milder form of these brain problems.   NMDAr is slowing down brain activity, that'S the key point.  So, in my hypothesis, I see this a a continuous spectrum, but serious and chronic mental condition like psychosis would be at the other end of the spectrum.
if you look in the diagram at https://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory , see, on the bottom, that a raise in KYNA (kynyrenic acid), through the action of KYN, is shown to first produce u follow the arrows, you see that these cognitive deficits combined with emotional symptoms like depression, anxiety and impulsivity, lead to more severe conditions.   Chronic mood disorders, for example, appears to me as very common among our members.

Supplementing for tryptophan is sure a good idea, and I do it as well, because it applies as well to the other branch of the kynurenine pathways,the quinolinic acid pathway ( the one I think I suffer from and causes me much emotional symptoms).   I eat some pumpkin seeds every day, for example.   I also avoid too much BCAA ( branched chain amino-acids), which compete with TRP for ontering the brain ( same molecular transporte thourgh the BBB).

For me, having no cognitive symptoms, and much anxiety and emotional symptoms, I use NMDAr blockers, but I guess that someone having cognitive issues may test some safe and natural NMDAr antagonists, like huperzine-A  ( actually, some members had results with it for cognitive symptoms.... I cannot say, since I have absolutely zero cognitive symptoms, so cannot test this).

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