Hypersensitivity Megathread

[Muon]

Ok then it probably does not play a role in pois.

[Nas]

Ok then it probably does not play a role in pois.

I've also tried L-Dopa and it seems to be good but it's not fundamental. I don't what we're missing or what what's happening to the brain but I think we can prevent it if we figure it out.

[Muon]

I don't what we're missing or what what's happening to the brain but I think we can prevent it if we figure it out.

Good luck with that

[Nas]

I don't what we're missing or what what's happening to the brain but I think we can prevent it if we figure it out.

Good luck with that

Why?

[Muon]

I wished you good luck for trying to figure it out. I'm disengaging from this discussion because it's not leading to anything and I'm out of ideas. You may ask other people for their ideas on causes of brain related symptoms in pois.

[Nas]

I wished you good luck for trying to figure it out. I'm disengaging from this discussion because it's not leading to anything and I'm out of ideas. You may ask other people for their ideas on causes of brain related symptoms in pois.

Oh, sorry I thought you were sarcastic lol.

[Vandemolen]

I think Muon is in the right direction. I got POIS in 2000. At the same time I developped a sensitivity for perfume and cigarette smoke. A lot of symptoms are the same: red itchy eyes, runny nose, irritation in the throat. Of course there are more POIS-symptoms. But I think POIS is a multiheaded monster. One of the causes could be hypersensitivity. And in my case my POIS is even worse when I have a sexual activity without ejaculation. If I only get POIS after ejaculation then you could say it is a hormone thing. And there are other members who also get POIS even without orgasm. But I am not saying hormones are not involved, because there are POIS-patients who get relief by testosterone. And maybe there is not only 1 type of POIS.

[Muon]

Hi Vandemolen,

There are actually more than two subtypes of type IV hypersensitivity. I have added these to the first post, just scroll down: https://poiscenter.com/forums/index.php?topic=2925.msg27479#msg27479

They are mentioning the possibility of patients having multiple subtypes where one is dominant over the other. Perhaps different poisers have different type IV subtypes. I also got IL-8 elevated, if I test positive for GM-CSF then there might be a chance I got subtype IVd. Increase in Interferon gamma could already be an indication for type IV HS in general though.

I remember that Nanna once mentioned that I should be tested for GM-CSF. A delayed type VI HS does exist as well but haven't read about that yet, they also propose a seventh type in a paper. 

[Vandemolen]

Maybe you should post it in the blood test discussion topic. If some guys do blood tests they can check also if they might have type IV HS. At short time I can not do blood tests. But I hope to able to do it about a few weeks or months.

[Muon]

The lymphocyte transformation test might be a method for measuring a cellular T-cell response to seminal fluid. Even more interesting is to combine this with gel electrophoresis.

https://www.imd-berlin.de/en/special-areas-of-competence/lymphocyte-transformation-test-ltt.html
https://en.wikipedia.org/wiki/Gel_electrophoresis

I might ask the medlab in Berlin whether it's possible to use this test in combination with my seminal fluid. So what you can do is using this test on a pois group and compare it with healthy controls. You could repeat the test with gel electrophoresis to explore properties of the molecule like size.

[Nas]

Th1 activation ---> interferon gamma release ---> increased macrophage activity ---> release of hydrolytic enzymes ---> affecting neurotransmitter metabolism ---> cognitive dysfunction

Perhaps POIS symptoms are being caused by the release of a bunch of enzymes damaging tissue which mimicks inflammation or altering enzyme activity in general.

I've read somewhere that certain Cytokines can mess with the kynurenine pathway leading to psychological issues. If anyone can find these papers you'd make me a favor. Maybe type 4 hypersensitivity leads to production of certain Cytokines that mess with neurotransmitters production.

[Muon]

Maybe poisers show different cytokine profiles Nas, these could affect parts of the brain. We need to take this step by step. The first step is to prove whether this is a type IV HS by using the LTT. Waldinger mentioned in his paper that a flu-like state could be caused by cytokines. I think it's possible that different symptom clusters might be caused by different cytokine profiles. I will send an email to the lab and ask whether it's possible to use my seminal fluid for LTT.

[Nas]

Again I'm more focused on the cognitive side of things. Let's assume that these brain effecting Cytokines are elevated in POIS. What would be the mechanism? If anyone has an idea please share.

[Muon]

I'm more focused on trying to prove T-cell mediated hypersensitivity in pois, this is what the thread is about. You are getting two steps ahead. You could search for papers which related cognitive symptoms to cytokines. I've mentioned a few cytokines for the subtypes in the first post of this thread, you can look up if they play a role in cognitive dysfunction. Just to let you know, I'm not going into all of that, not in the mood for that (at least for now).

[Nas]

I'm more focused on trying to prove T-cell mediated hypersensitivity in pois, this is what the thread is about. You are getting two steps ahead. You could search for papers which related cognitive symptoms to cytokines. I've mentioned a few cytokines for the subtypes in the first post of this thread, you can look up if they play a role in cognitive dysfunction. Just to let you know, I'm not going into all of that, not in the mood for that (at least for now).

Not trying to interfere with this thread Muon. But one last point I like to make, is that by knowing which Cytokines interfere with brain metabolism I can narrow down the possible subtypes. So again if anyone has any knowledge of these Cytokines please tell.

[certainlypois2]

I'm more focused on trying to prove T-cell mediated hypersensitivity in pois, this is what the thread is about. You are getting two steps ahead. You could search for papers which related cognitive symptoms to cytokines. I've mentioned a few cytokines for the subtypes in the first post of this thread, you can look up if they play a role in cognitive dysfunction. Just to let you know, I'm not going into all of that, not in the mood for that (at least for now).

Not trying to interfere with this thread Muon. But one last point I like to make, is that by knowing which Cytokines interfere with brain metabolism I can narrow down the possible subtypes. So again if anyone has any knowledge of these Cytokines please tell.

Quantum did a write up on cytokines on this thread: https://poiscenter.com/forums/index.php?topic=2350.msg19559#msg19559
It will also be a good place to continue cytokine discussion

[Muon]

Delayed hypersensitivity and negative PGE feedback loop:
Regulation of allergic responses by prostaglandins: a review

Antigen--->sensitized lymphocytes--->lymphokines--->stimulation of macrophages--->macrophage activation--->PGE--->lymphocyte inhibition.
''This negative feedback system has been suggested as a device for regulating the extent and duration of lymphocyte activation in delayed hypersensitivity reactions''

https://en.wikipedia.org/wiki/Lymphokine
From that list IL-3,5 and GM-CSF haven't been measured. IFN-g rises this could activate macrophages which could release PGE molecules on their turn inhibiting lymphocytes and causing a delayed reaction. The PGE series could be explored.

[Muon]

All those speculations in papers about hypersenstivities and potential involvement of cytokines and not a single doctor measuring cytokines...mind blowing!

[Muon]

Human Lymphocyte Migration as a Parameter of Hypersensitivity
So does that mean we have to block T-lymphocyte migration?
Symptom localization in POIS = higher density of T-lymphocytes to inflammatory sites by migration?

Some quick examples:
Astilbin suppresses delayed‐type hypersensitivity by inhibiting lymphocyte migration

''Repertaxin also selectively blocked CXCL8-induced T lymphocyte and natural killer (NK) cell migration.''
Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2

Idea for POIS: Look for medicine that can block T-lymphocyte migration and adhesion or block lymphokine production.

[Nas]

Human Lymphocyte Migration as a Parameter of Hypersensitivity
So does that mean we have to block T-lymphocyte migration?
Symptom localization in POIS = higher density of T-lymphocytes to inflammatory sites by migration?

Some quick examples:
Astilbin suppresses delayed‐type hypersensitivity by inhibiting lymphocyte migration

''Repertaxin also selectively blocked CXCL8-induced T lymphocyte and natural killer (NK) cell migration.''
Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2

Idea for POIS: Look for medicine that can block T-lymphocyte migration and adhesion or block lymphokine production.

Good find