Long-Distance Interferon Signaling: Could It Explain ME/CFS?

Hip

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I came across an interesting article and study about long-distance interferon signaling.

Long-distance interferon signaling is where a viral infection just outside the brain, such as in the olfactory bulb, will trigger a signal which is sent to all the neurons inside the brain, warning of the infection, and instructing the neurons to make antiviral type I interferons, so that the neurons are prepared for the infection, and thus don't get infected.

This signal provides an advanced warning that a virus is present at the brain's periphery, and the signal saves the brain from suffering a major infection.

The mechanism of signaling is not yet known: but we know some sort of signal is transmitted across the entire brain that triggers interferon release in the brain cells.

On reading this, it occurred to me that this signaling mechanism might be involved in ME/CFS:

It is known that type I interferons cause the symptoms of sickness behavior and cognitive dysfunction (see here), which are similar to ME/CFS symptoms. So I was thinking: what if there were a chronic infection just outside the brain: this might trigger persistent long-distance interferon signaling, causing the neurons of the brain to constantly release interferon, thereby resulting in ME/CFS-type symptoms.


This idea is similar to the chronically infected vagus nerve hypothesis of ME/CFS, which was proposed by Dr Michael VanElzakker.
 
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Wishful

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It looks like a possibility, but needs a lot more investigation. My interest has been more on IFN-gamma, while this study focuses on alpha/beta.
 

Hip

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Long-distance interferon signaling could explain the cases of chronic fatigue that are improved or cured after nasal or sinus surgery, I am thinking.

If you have an inflamed and infected nose or sinuses, then conceivably this infection/inflammation may trigger long-distance interferon signaling, inducing the release of interferon throughout the brain, thereby causing fatigue and cognitive symptoms.



And maybe nasal or sinus inflammation in regular ME/CFS patients could contribute to their fatigue and cognitive symptoms, via a long-distance interferon signaling mechanism.

I know that ever since I caught the virus which triggered my ME/CFS, my nose has been mildly inflamed and feels bunged up. There is rarely a day where my nasal air passages are clean as a whistle; they always feel slightly bunged up.

Plus I have post-nasal drip, which means the sphenoid sinus is constantly producing mucus, suggesting this sinus cavity may be inflamed or infected. The sphenoid is located right next to the pituitary gland of the brain, and maybe an infection in the sphenoid might trigger long-distance interferon signaling, worsening ME/CFS symptoms. Fatigue is a known symptom which can be present in post-nasal drip.
 

Hip

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I am also wondering whether long-distance interferon signaling is achieved via a chemical (molecular) signal, or by an electrical nerve signal. Nobody yet knows how this signal is transmitted.

In the case of the olfactory bulb where long-distance interferon signaling was demonstrated, you have a direct nerve route from the olfactory bulb into the brain: olfactory nerve (the first cranial nerve).

So conceivably the signaling could be achieved via a nerve signal transmitted along the olfactory nerve. Or alternatively it might be achieved by a chemical secreted by the olfactory bulb. But this seems less likely, because this chemical would first have to get into the brain, and then secondly spread to the entire brain, if it is to warn all neurons in the brain of the presence of an infection at the brain periphery.

So it seems more likely that long-distance interferon signaling will be transmitted by a nerve signal.
 

Hip

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Super interesting, I think this may be related to Vaccine-triggered CFS linked to nasopharyngitis.
Very true! Good thinking!

I guess any local area of infection or inflammation, especially if close to the brain, might potentially induce long-distance interferon signaling, and thus ME/CFS-like symptoms.

I guess those jawbone cavitation infections which occasionally lead to ME/CFS could be another example of an infection close to the brain which might induce long-distance interferon signaling (see the threads Cavitations and root canals and My recovery story).


The the idea that a hidden local infection could be the cause of many chronic diseases (focal infection theory) was proposed over a 100 years ago, but fell out of favor. However there has been a small a revival in the ideas of focal infection in recent decades.
 
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And maybe nasal or sinus inflammation in regular ME/CFS patients could contribute to their fatigue and cognitive symptoms, via a long-distance interferon signaling mechanism.

I know that ever since I caught the virus which triggered my ME/CFS, my nose has been mildly inflamed and feels bunged up. There is rarely a day where my nasal air passages are clean as a whistle; they always feel slightly bunged up.
I've been saying some version of this exact thing for years now.

In my case- I experience a type of daily inflammatory cycle which is centered- up in my sinuses- and just on the other side of that area is: all the key areas of our brain.

But in my case- I experience severe dryness. Sahara desert. No mucous in my sinuses at all- they dry out and close off- up back- something swells. It feels pinched close. This swelling- occurs daily, less on a good day.

My tonsils and adenoids were removed at 10. If feels- like where adenoids might have once dwelled.

****

My eyes pour most of the time- in stark contrast to the rest of it all being dried out. Severely affecting my vision.

My eyes are very very ill.

Between my throat and sinuses and tongue and palette and teeth squeezing out of my head- my tongue developes hornes on the side each nite (I will forgo discussing the horror of what my. tongue reports to the chinese herbalist).

My tongue swells up at night so much- it does;t fit any longer.

Angiodema-type symptoms maybe. Mast Cell. Untreated.
 

Treeman

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I know that ever since I caught the virus which triggered my ME/CFS, my nose has been mildly inflamed and feels bunged up. There is rarely a day where my nasal air passages are clean as a whistle; they always feel slightly bunged u
I suffer this too as a symptom. I had viral meningitis in 99 (This bout of ME started 93) . My lymph nodes in my throat are constantly swollen and I have asthma. I recently started taking 0.5g daily of Colchicine and my asthma has almost disappeared and I can breath the best I have for almost 3 decades. I'm not sure if any of my other symptoms have cleared, I'm still monitoring it! I plan on increasing the dose to 2 tabs a day as soon as my sleep settles. It always becomes disturbed when ever I take new medication/supplements but I've also got a little emotional stuff going on so it may be that disturbing the sleep?
 

sometexan84

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That's interesting. I remember looking into this type of persistent signaling.

The link to the 1st article below talks about "chronic IFN-I signaling, immune suppression and viral persistence".

After seeing that I tried to see if there was treatment for that. See the 2nd link below. "Anifrolumab, a drug that binds to type 1 interferon receptors and stops the molecule from overstimulating the immune system"
 

Treeman

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After seeing that I tried to see if there was treatment for that. See the 2nd link below. "Anifrolumab, a drug that binds to type 1 interferon receptors and stops the molecule from overstimulating the immune system"
Used to treat Lupus, interesting, I've got low amounts of antinuclear antibody that cause Lupus in high doses.
 

Prefect

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@Hip Is your nose Still stuffed up? I vaguely remember you mentioning on one thread that you managed to eliminate nasal stuffiness using NAG...?
 

Hip

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@Hip Is your nose Still stuffed up? I vaguely remember you mentioning on one thread that you managed to eliminate nasal stuffiness using NAG...?
It's something which comes and goes. These days it's only a relatively mild feeling of bunged up airways I have in my nose. They are not bunged due to mucus as far as I am aware, but I imagine due to slightly inflamed (and thus slightly swollen) mucous membranes in the nose, which will narrow the airways.

I found certain supplements will reduce or eliminate this bunged up stuffiness, including NAG, and I listed those supplements in this post.