Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

[Wishful]

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0259-2

I came across this article and thought that some here might be interested. It's not specific to ME, but does include it. The summary is:

"It is concluded that peripheral inflammation and immune activation, together with the subsequent activation of glial cells and mitochondrial damage, likely account for the severe levels of intractable fatigue and disability seen in many patients with neuroimmune and autoimmune diseases.This would also appear to be the case for many patients afforded a diagnosis of Chronic Fatigue Syndrome."

It's a very long and complex paper, not something I can follow easily. A quick browse showed discussion of positive feedback loops, where inflammation feeds back to cause more inflammation, which seems to be occurring in ME.

 

[Wishful]

If you liked that paper, you might also like: https://link.springer.com/article/10.1186/s12916-015-0310-y Titled: "The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders" Seems similar at a quick glance.

 

[andyguitar]

I dont think the authors of the first paper you posted have a very good understanding of what cfs is. They seem to think its about fatigue.

 

[Wishful]

I think we had an earlier discussion about how poorly defined 'fatigue' is. I think my 'fatigue' is caused by brain cells not working quite right, which is in line with what they're talking about.

 

[ljimbo423]

I haven't read the whole paper yet but this statement rings a very loud bell of truth to me-

O stands for Oxidative stress and NS stands for Nitrosative stress-

Indeed, the production of proinflammatory cytokines and other inflammatory molecules by macrophages and other sentinel cells, even in the absence of pathogen invasion, and the subsequent activation of NF-kappaB are early events in the genesis of chronic inflammation [40,41].

Activation of this transcription factor leads to the upregulation of cytokines and O and NS [6,42-44]. These players can engage in a feed-forward manner to maintain and amplify chronic inflammation and immune activation in a TLR radical cycle [4].

 

[Wishful]

I did notice that part. What I don't understand is why antioxidants and peroxynitrite scavengers increase my ME symptoms. If O and NS were important parts of causing ME symptoms, Resveratrol, cinnamon, turmeric and rosemary should decrease my symptoms. There could be non-obvious complications, but it certainly doesn't convince me that O and NS are responsible for the symptoms

 

[ljimbo423]

I did notice that part. What I don't understand is why antioxidants and peroxynitrite scavengers increase my ME symptoms. If O and NS were important parts of causing ME symptoms, Resveratrol, cinnamon, turmeric and rosemary should decrease my symptoms. There could be non-obvious complications, but it certainly doesn't convince me that O and NS are responsible for the symptoms

I agree. I don't think O and NS can be at the root of ME/CFS. That was one of my first thoughts. If O and NS are causing this illness, than high enough doses of antioxidants should stop the cycle. Yet many people have and are taking very high doses of antioxidants but are still sick.

I do think that immune system activation, O and NS, mitochondrial dysfunction and low grade brain inflammation do, to some extent, keep this illness locked in place but are not the root cause.

 

[ebethc]

do either of these papers shed light on possible testing for CFS? This section in particular makes me wonder where we are in testing... (ROS and nitrogen species, etc.)

"This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines."

 

[Rufous McKinney]

I dont think the authors of the first paper you posted have a very good understanding of what cfs is. They seem to think its about fatigue.

Thinking about my prior supervisor, who was diagnosed with Lupus at 20, took some pill that is considered dangerous...took it anyway...and so She Just Kept Going and Going....Her batteries never run out.

I am a wallflower, wilting for 50 years...and she has Lupus and ...oh doesn't sunbath.

 

[xebex]

I did notice that part. What I don't understand is why antioxidants and peroxynitrite scavengers increase my ME symptoms. If O and NS were important parts of causing ME symptoms, Resveratrol, cinnamon, turmeric and rosemary should decrease my symptoms. There could be non-obvious complications, but it certainly doesn't convince me that O and NS are responsible for the symptoms

There is some evidence that too much antioxidants can actually cause oxidative stress themselves. It is my belief that the ME body is highly sensitive to fluctuating levels of anything (hormones, neurotransmitters etc) going even slightly up and down, it’s why our doc says we aren’t hypoglycaemic when we have all the symptoms of hypoglycaemia - the tests show normal but our body/brain freaks out at even the slightest change. https://www.abc.net.au/news/health/2017-04-21/can-you-have-too-many-antioxidants/8457336

 

[ebethc]

There is some evidence that too much antioxidants can actually cause oxidative stress themselves.

exactly! this is so confusing, b/c what is "too much" anyway?

It is my belief that the ME body is highly sensitive to fluctuating levels of anything

yes, I have always been super sensitive to weather changes and weather extremes... it's like my body has a hard time achieving/maintaining homeostasis..... I don't have POTS, but I think this dynamic in my own body is similar to POTS at a meta level... I don't know what it means, but it sure seems like it could be a brain stem problem...

 

[xebex]

@ebethc absolutely, I don’t have diagnosed POTs either but if I crash really hard I will have classic pots symptoms that go away if I rest for a week. Luckily I’m not plagued with 24:7 POTs but just standing is enough to trigger a crash I just don’t get those typical POTs symptoms most of the time. I believe autonomic dysfunction is just one part of ME and it might not present like classic autonomic dysfunction but that is still what it is.

 

[HABS93]

I haven't read the whole paper yet but this statement rings a very loud bell of truth to me-

O stands for Oxidative stress and NS stands for Nitrosative stress-

This is exactly what I believe is causing not just fatigue in my sarcoidosis (Immune system overreacting ) but causing depression and anxiety with the disrupted nerutransmitters the cyctokines cause when entering BBB. I'm just having trouble understanding exactly what that means and how do you even solve this .

 

[ebethc]

"...with many studies reporting a significant positive correlation between markers of oxidative stress and symptom severity."

what are the tests called that find/measure markers of oxidative stress?