TH1 TH2 flipflopping controlled by the brain? I think maybe yes

[osisposis]

ok, I brought this up on another thread, once th2 allways th2? or flipflopping back and forth between th1 and th2, because looking at GWI witch I relate too, and have followed research there, witch resently was found that many GWI Vet's that were diagnosed with PTSD has resently been found to have TBI because of chemical exposures newly termed TBI/PTSD, who do suffer off and on depression and mood events, like me, and I was also diagnosed with PTSD after my water damaged house exposure that tried to kill me.
now for long time there was debate on th1/th2 and weither theres flipflopping between the two stages or once th2 allways th2. prob still some debate but I think it's very possible that those that have tipped to th2 are now flipfloppers, this is about environmental exposures causing ME/CFS.
I think th1/th17 profile that is well known to be involved in environmental exposures and the tipping point to th2 and likely high affinity IgE , "allergies" ( points to infection and autoimmunity) may have to be looked at differently now as th1 has also pointed to autoimmunity. so ya, I'd say we are flip flopping .
was thinking about Jarred Younger beliefs that this is all about the brain, it appears to be looking so with CFS and FM. but maybe it's not so for all ME/CFS'ers because not all of us are here from environmental exposure. and not all have the severe sinus, olfactory,amygdala,>limbic involvement from inhalation of chemicals/toxins. having severe CNS FM , you'll know it, that kindling in the brain is major event, this goes way beyond brain fog, symptoms this is TBI.
some may have secondary effects to these areas from involvement from the brain from gut /brain , leaky gut, but you may get diagnosed with PTSD as I did but that itself is a symptom of TBI (closedhead TBI caused by chemical exposures) so anyways I just looked to see if the debate on th1 th2 had resolved, but I added the brain to my search and this came up, haven't looked much farther into it yet but another article caught my eye as well.

Th1, Th2, and Th3 cytokine alterations in major depression.
http://www.ncbi.nlm.nih.gov/pubmed/16126278


Differential gene expression in brain and peripheral tissues in depression across the life span: A review of replicated findings.
http://www.ncbi.nlm.nih.gov/pubmed/27565517

 

[osisposis]

Transl Psychiatry. 2016 Jun 14;6(6):e839. doi: 10.1038/tp.2016.101.

Epigenetic differences in monozygotic twins discordant for major depressive disorder.


Network analysis revealed genes and gene networks that support the inflammation hypothesis of MDD.

http://www.ncbi.nlm.nih.gov/pubmed/27300265

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931599/

Blood-based gene expression signatures of medication-free outpatients with major depressive disorder: integrative genome-wide and candidate gene analyses.
http://www.ncbi.nlm.nih.gov/pubmed/26728011

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700430/

The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder.
http://www.ncbi.nlm.nih.gov/pubmed/24886127

 

[taniaaust1]

osisposis, would you mind breaking your first post into paragraphs so those of us who struggle with reading can read it. I'd like to be able to read it.

thanks

 

[J.G]

Not sure if the Th1/Th2 question in ME/CFS has been resolved, but Hornig's presentation on cytokine levels (here) in short-term and long-duration PWME revealed some interesting findings. IIRC, pro-inflammatory cytokines are sharply upregulated in <3 year ME, to be replaced by full-on immune dysregulation after that marker. I'm not sure this amounts to a Th1/Th2-shift, but it could indicate that the body succeeds at shutting down a runaway Th1-response (to protect the brain, maybe?). This shutdown mechanism could then cause the immune dysregulation (the 'flip-flopping') in longer-duration patients.

 

[osisposis]

Not sure if the Th1/Th2 question in ME/CFS has been resolved, but Hornig's presentation on cytokine levels (here) in short-term and long-duration PWME revealed some interesting findings. IIRC, pro-inflammatory cytokines are sharply upregulated in <3 year ME, to be replaced by full-on immune dysregulation after that marker. I'm not sure this amounts to a Th1/Th2-shift, but it could indicate that the body succeeds at shutting down a runaway Th1-response (to protect the brain, maybe?). This shutdown mechanism could then cause the immune dysregulation (the 'flip-flopping') in longer-duration patients.

Thanks, I've looked at this before and I can realte to that but , ugg, so much to try to soak in it's been shown the the brain goes into hibernation mode to protect from further damage with TBI, , where basicly if I understand right may be playing in with innate dysfunction or supression, maybe also because of lack of autophagy, lipid rafts, maybe autophagy is required to bring one out of hibernation mode. uggg, just trying to wrap my brain around how all this plays together but been distracted by so much new info. all at onces and there my brain just having a very hard thing making connections in my head or all this

 

[osisposis]

so maybe the hibernation plays in in the early part but not the later, but if infection in the brain is triggering hibernation and we deal with reaccuring infections than possabily we are flipflopping back and forth

 

[J.G]

I struggle too. We'd probably relish the complexity if our own health wasn't on the line

Anyway, I see brain damage more in terms of steady neuronal degeneration, particularly of serotonergic and dopaminergic neurons, due to persistent assault by pro-inflammatory cytokines and assorted immune cells. It is known that both 5-HT and DA neurons are very sensitive to prolonged inflammatory stimuli, which sparks die-off.

Consider also that the brain is our most valuable organ. As such, the body strives to protect it all costs under all circumstances.

So when I think about the evolving pathology of ME/CFS (i.e. from a pro-inflammatory Th1 response to immune dysregulation), I think of it in terms of neuronal health. HPA axis glucocorticoids are supposed to rein in the inflammatory Th1 response, but in early ME pathology, they're not accomplishing this (for whatever reason). So if the body wants to limit neuronal damage, it must come up with a non-routine, radical way of shutting down the inflammatory response wholesale. 'Dauer' is probably a result, or perhaps aspect, of this last-ditch effort.

 

[osisposis]

TGF beta-1 is interesting, I haven't researched it much but remember it in my research, looking at the FM side of this , what I relate to sinus brain involvement, and it's connection to depression, and involvement in the brain.

Th1, Th2, and Th3 cytokine alterations in major depression.
The Th1 and Th2 cytokine imbalance was observed in subpopulation of depressed patients. TGF-beta1 seemed to play a role in the pathophysiology of depression in this population. Moreover, antidepressant treatment was found to affect the Th1/Th2 balance through the action of TGF-beta1.
http://www.ncbi.nlm.nih.gov/pubmed/16126278

https://ghr.nlm.nih.gov/gene/TGFB1
http://atlasgeneticsoncology.org/Genes/TGFB1ID42534ch19q13.html

The TGFB1 gene provides instructions for producing a protein called transforming growth factor beta-1 (TGFβ-1). The TGFβ-1 protein helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). The TGFβ-1 protein is found throughout the body and plays a role in development before birth, the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. TGFβ-1 is particularly abundant in tissues that make up the skeleton, where it helps regulate bone growth, and in the intricate lattice that forms in the spaces between cells (the extracellular matrix). Within cells, this protein is turned off (inactive) until it receives a chemical signal to become active.

TGF-β1 is a growth factor ubiquitously expressed. It was initially discovered as a factor inducing colony formation of normal rat kidney fibroblasts in soft agar in the presence of epidermal growth factor (EGF) (Roberts et al., 1980; Roberts et al., 1981). By immunohistochemical techniques TGF-β1 was strongly detected in adrenal cortex, megakaryocytes and other bone marrow cells, cardiac myocytes, chondrocytes, renal distal tubules, ovarian glandular cells and chorionic cells of the placenta and also in cartilage, heart, pancreas, skin, and uterus (Thompson et al., 1989).

 

[osisposis]

when I got ill from that water damaged house I couldn't tolerate much on anything at all and drugs, inhalers, antibiotics,pain killers, and others caused horrable reactions, what was very interesting is that I was given Clonazepam for anixity, now I only had to take half of I think was a 20mg. may of been 10 or 15, cant remember now, I've had some weird reactions to drugs, my body and brain was so missed up it amased me that half of one of these knocked me out and I'd sleep like 14-18 hours, now theres something about how this worked in my brain that may be of some benefit to others.