Discriminatory cytokine profiles predict muscle function, fatigue and cognitive function in patients with Myalgic Encephalomyelitis/CFS

[Ski_again]

Here's my TH1/TH2 panel from Labcorp. IL-4 is 25x the top of the range, and TGF-1b is 2x.

This shows I am TH2 dominant, while TH1 looks a bit suppressed.

 

[Learner1]

Have you found what's driving them? It might lead to something treatable.

IL-4 is related to allergy, mast cell, and autoummunr diseases, as well as neurological diseases like Alzheimer’s MS, and glioblastoma multiforme.

According to Self Decode, TGF-beta plays an important role in autoimmune diseases, food intolerances, cancer, cognitive function, wound healing and other diseases. It has pro- and anti-inflammatory effects, and:

• Causes collateral damage in infections
• Causes the growth/changes in tissue
• Decreased acetylcholine
• Decreased slow wave or deep sleep
• Decreases muscle regeneration
• Decreases the action of the vitamin D receptor
• Increases free radicals
• Can decrease bone density
• It inhibits proliferation of most other cell types
• Suppresses red blood cell formation and lymphocytes (T and B cells)
• Suppresses antibody production
• Suppresses Cytotoxic T Cell (CD8) and Natural Killer cell activity...this can cause viral infections to get out of control.
• Deactivates macrophages
• Promotes oral tolerance
• Suppresses inflammation
• Promotes wound healing and new blood vessel formation (angiogenesis)
• Induces local inflammation and fibrosis
• Stimulates extracellular matrix deposition
• Promotes switch to IgA
• Can increase cancer growth
• Cause negative changes in the airways
• Can benefit cognitive function (when very mildly elevated)

 

[Muon]

Do you have suggetsions on how to lower these markers?

No I'm not aware of a golden bullet but some Flavonoids can lower cytokines, maybe you can find something in here: MCAD treatment

Regarding parameters at IMD Berlin; I believe you can organize private studies at IMD via Synevo. Parameters which indicate 'Batch analysis' are multi sample test kits: https://www.imd-berlin.de/nc/leistungsverzeichnis.html

It's cheaper when you are able to get a group of patients together.

 

[Judee]

This article says, "β-Boswellic acid can downregulate the synthesis of prostaglandins by inhibiting COX-1 in intact human platelets (Siemoneit et al., 2008). It has been shown that β-boswellic acid inhibits the production of pro-inflammatory cytokines, including TNF-α, IL-1, IL-2, IL-6, IL-12, and IFN-γ, by suppressing the activation of NF-κB (Gayathri et al., 2007)."

Don't know if that helps. Ken Lassesen says it also works as a "poor man's heparin." https://cfsremission.com/treatment/...n-fog/boswellia-neuroprotective-and-anti-ebv/

He talks a lot on his site (like here) about ME/CFS people having hypercoagulation issues as well. Not sure if that is related to the increased cytokines though.

 

[Ski_again]

Have you found what's driving them? It might lead to something treatable.

IL-4 is related to allergy, mast cell, and autoummunr diseases, as well as neurological diseases like Alzheimer’s MS, and glioblastoma multiforme.

According to Self Decode, TGF-beta plays an important role in autoimmune diseases, food intolerances, cancer, cognitive function, wound healing and other diseases. It has pro- and anti-inflammatory effects, and:

• Causes collateral damage in infections
• Causes the growth/changes in tissue
• Decreased acetylcholine
• Decreased slow wave or deep sleep
• Decreases muscle regeneration
• Decreases the action of the vitamin D receptor
• Increases free radicals
• Can decrease bone density
• It inhibits proliferation of most other cell types
• Suppresses red blood cell formation and lymphocytes (T and B cells)
• Suppresses antibody production
• Suppresses Cytotoxic T Cell (CD8) and Natural Killer cell activity...this can cause viral infections to get out of control.
• Deactivates macrophages
• Promotes oral tolerance
• Suppresses inflammation
• Promotes wound healing and new blood vessel formation (angiogenesis)
• Induces local inflammation and fibrosis
• Stimulates extracellular matrix deposition
• Promotes switch to IgA
• Can increase cancer growth
• Cause negative changes in the airways
• Can benefit cognitive function (when very mildly elevated)

Unfortunately my physicians haven't taken any interest in these results, since they aren't directly diagnostic of anything (no surprise) nor point to any intervention.

I love SelfDecode, but it's a bit of an auto-populated data dump, and all the references cited for any associations need to be read and validated before you can draw any conclusions.

@Muon, I've got a browser tab open with the MCAD link and I'll see if it leads anywhere.

Hopefully more people will post their results to this thread and we can find come common associations.

 

[Muon]

@mitoMAN If mast cells are firing then eosinophils are probably activated as well. You could check for eosinophil cationic protein (ECP) at IMD, it's a unique molecule for eosinophils.

 

[mitoMAN]

@mitoMAN If mast cells are firing then eosinophils are probably activated as well. You could check for eosinophil cationic protein (ECP) at IMD, it's a unique molecule for eosinophils.

Yes my ECP is also elevated above maximum but not as severely as VEGF for example.
ECP: 28.7yg/L Reference: <18.0

I have tried most of standard medications for MCAS.
H1 H2 Blocksers
Mirtazapin, Amitryptilin, Ketotifen, Montelukast, Vitamin C, Quercetin, ASS, Cromolyn Sodium, Cerebrex.
Nothing really helped much.

Lorazepam seems to help a bit.
I also have ADD and my friend suggested trying very low dose Amphetamine to stabilize Mastcells.
It does wonders for him at 5mg. He also has ADHD.

My Histamine is always sky rocket high, so are Leukotrienes. Histamine Intolerance was checked and its not the case for me.

 

[Muon]

Viral products act on certain TLRs. You need to look up which ones and could target those: Mast cell receptors and their agonists

Diazepam could be taken for IL-8.
Dexamethasone could give a rapid response if IL-33 is involved. CBD could be tried.

Certain hormones can inhibit MCs like testosterone (TRT) and progesterone.

Tranilast?

From Goldstein's book 'Tuning The Brain' (not sure how they affect mast cells):

"Amphetamine salts (Adderall) are superior to dextroamphetamine and need only be administered twice a day."

"Guanfacine has been found to be as effective as dextroamphetamine in the treatment of ADHD in adults (Taylor FB, Russo JR, 2001). It is a specific agonist at the alpha2AR, which is particularly abundant in the PFC and LC."

"The first plausible explanation about the mode of action of amphetamine in ADHD is that inhibition of DA firing and activation of negative feedback mechanisms increases DA release by stimulating NE release. Alpha1 heteroceptors on DA neurons stimulateDArelease (Zametkin AJ, LiuttaW, 1998). D1 and D2 antagonists do not affect amphetamine-induced stimulation, nor do alpha2 antagonists or beta blockers (ShiWXet al., 2000). Alpha1 antagonists block amphetamine-induced burst responses and diminish increase in firing rate. I should be able to administer the alpha1 agonist midodrine to a patient and see the same response as I do with dextroamphetamine. My patients who have obtained the NE-reuptake inhibitor reboxetine should also have a similar effect, but they do not."

 

[Muon]

@mitoMAN I recall that Melatonin is able to decrease VEGF. I have read it somewhere in literature, can't remember which paper it was.

 

[mitoMAN]

I noticed that the immunemodulator THYMOGEN is a VEGF inhibitor I will be testing soon.


Oglufanide (H-Glu-Trp-OH) is a dipeptide immunomodulator isolated from calf thymus. Oglufanide inhibits vascular endothelial growth factor (VEGF). Oglufanide can stimulate the immune response to hepatitic C virus (HCV) and intracellular bacterial infections.

https://www.medchemexpress.com/Oglufanide.html

Thank you for all your great input.
Ketotifen turned out to be a great MCAS blocker for me.

 

[mitoMAN]

@mitoMAN If mast cells are firing then eosinophils are probably activated as well. You could check for eosinophil cationic protein (ECP) at IMD, it's a unique molecule for eosinophils.

Can ECP be taken as an additive MCAS marker? Never saw it listed together.
My Tryptase was always negative

 

[Muon]

Can ECP be taken as an additive MCAS marker?

No

Regarding targeting both mast cells and eosinophils, see the Siglec-8: Mast cell Biology and Clinical Targeting section: Proceedings from the Inaugural American Initiative in Mast Cell Diseases (AIM) Investigator Conference

 

[gbells]

Cytokines are just effects following tissue damage not causes so this won't cure ME. They are raised by lots of things (red meat, high inflammation diet, dysbiosis in the gut).

 

[Wishful]

Cytokines are just effects following tissue damage not causes so this won't cure ME.

Has no one bothered to try injecting (or pills if possible) the various cytokines into PWME to see whether a specific one is responsible for triggering symptoms? It seems like a reasonable approach to me. It wouldn't require mega-doses, just the level normally created by infections, red meat, etc. I'm sure there's be volunteers for something that might help in understanding ME.

 

[gbells]

Has no one bothered to try injecting (or pills if possible) the various cytokines into PWME to see whether a specific one is responsible for triggering symptoms? It seems like a reasonable approach to me. It wouldn't require mega-doses, just the level normally created by infections, red meat, etc. I'm sure there's be volunteers for something that might help in understanding ME.

Or you can just change your diet. Good for health too. Don't forget adequate vitamin D3.

https://www.precisionnutrition.com/...42120-AllContacts-OptimizeImmunityInfographic

 

[Wishful]

Or you can just change your diet.

That wouldn't determine if a specific cytokine was involved with ME symptoms. Raising them individually (or in sets) would show whether that's part of the mechanism of ME. Dietary change might make a person feel a bit better, but it wouldn't increase understanding of what causes ME symptoms.

 

[ljimbo423]

Has no one bothered to try injecting (or pills if possible) the various cytokines into PWME to see whether a specific one is responsible for triggering symptoms?

I don't know if it's been done in ME/CFS. They use to use Interferon Alpha (IFN-a) injections to treat hepatitis C.

Many patients experienced flu-like symptoms, that were often debilitating and would put them in bed for hours or longer, after their injections. With massive fatigue and flu-like symptoms. I know someone that when through that treatment.

If I remember right, some of them even experienced what looked like ME/CFS from the Interferon treatment. I'm pretty sure there is at least one person here that happened to. She cleared her Hepatitis C but developed ME/CFS from the IFN-a treatment.

Maybe the Interferon caused sensitized microglia, as Jarred Younger thinks, or a more permeable (leaky) Blood Brain Barrier or something else that caused her ME/CFS.

I'm almost ceratin it's immune activation the triggers my ME/CFS flares. They feel exactly like the flu. The glands under my jaw get swollen and tender, I get a runny nose, congestion, often sneeze, have body aches and pains, etc. Just like a cold or a flu. A clear sign of increased cytokines.

 

[mitoMAN]

Im very interested to see PR Patients post more of their own cytokine profiles in this thread.

 

[gbells]

That wouldn't determine if a specific cytokine was involved with ME symptoms. Raising them individually (or in sets) would show whether that's part of the mechanism of ME. Dietary change might make a person feel a bit better, but it wouldn't increase understanding of what causes ME symptoms.

Neither will measuring cytokines in blood since they are nonspecific.

 

[Wishful]

Neither will measuring cytokines in blood since they are nonspecific.

That's why I didn't suggest measuring cytokines in blood. I suggested altering them to see what happens.

If you had a malfunctioning engine, one diagnostic approach is to measure as much as possible. You could go to enormous expense to do 3-D x-ray scans, bore holes through the engine for sensors, etc. Another approach is to treat the engine as a 'black box': you can manipulate some inputs and measure some outputs. Spraying some fuel or oxygen into the air intake, or changing the voltage and current of the ignition, could quickly (and inexpensively) determine whether the problem is in the fuel/air or ignition systems, or compression.

Injecting cytokines is the equivalent of spraying some fuel into the air intake. Does it increase the ME symptoms or not? If it does, focus funding on the immune system. If it doesn't, focus funding on other areas. You could spend the entire ME funding on measurements and not find the core dysfunction, because even that funding won't measure everything.