Innate Immune Changes in the Peripheral Blood

[WillowJ]

Hmm... I've also had asthma, following bronchitis. Several years before the first CFS symptoms appeared. Can inhaled cortisone affect the HPA axis or immune system?

I had what seemed like chronic bronchitis (I didn't go to the doc and complain of symptoms, as at that point I could keep up with things) following a near-drowning incident a couple years before I got ME. Didn't notice asthma much until later, though.

 

[Jonathan Edwards]

Would it be logical to try a short course of steroids as a rescue drug for crashes/PEM? Sometimes we don't fully recover from these.

Steroids are a bit like Mephistopheles - you pay the price of selling your body to the devil in the long term in many situations. It is very hard to judge which situations short courses of steroids are justified for. There certainly are some but it is not so much a matter of logic as careful monitoring. In the 1960s a lot of children had a lot of steroids for asthma until they found that the survival rate was actually worse. But short courses of high dose steroid for temporal arteritis can prevent blindness. My impression is that although ME crash symptoms may sometimes respond to steroid that may not always be true by any means.

 

[MeSci]

I use a positive α7 nAChR allosteric modulator.

What do you take, @lansbergen?

 

[lansbergen]

What do you take, @lansbergen?

You know. The immune modulator. You must be very brainfogged today not to remember that.

 

[MeSci]

Steroids for asthma seem to have played a part in my illness. I have since been diagnosed with chronic bacterial infections. Since that time I had to have a two course of prednisolone for severe asthma/lung symptoms and my health has once again worsened overall - although ALL the inflammatory symptoms in my body reduced so did my overall functioning which has not been regained. I am now left with no choice but to take high dose inhaled steroids.

For me steroids cause a good reduction in many symptoms (joint pain, ankle swelling, breathing, swollen lymph) but I alwsy feel much owrse M.E while taking them and usually crash. At one point I was left on too high a dose of inhaled steroids for 8 years (these are the 8 years I was in remission for so...?) and after some time I started to get more and more frequesnt infections and hormonal problems which cleared up gradually after I spent a year tapering it down. I sowre I would never take them again - but if you cant breathe - and I have some fibrosis in lung then what can you do?

I wonder if there is any connection between your ME symptoms worsening after steroids (does this particularly include less energy?) and the fact that, whilst many of my symptoms have improved on a leaky-gut regime, energy levels have not?

I'm assuming for this possibility that my improvements are due to reduced inflammation, and that this in turn is due to increased cortisol.

But I've hoped that my immune system is also slowly normalising, and that as it becomes more normal I will get some energy back. Of course that is an optimistic view, but the route I am taking is the only thing that has given me significant, fairly-sustained improvement so I am sticking with it for now!

But I don't think that there can be a direct analogy with exogenous steroids, which of course have the potential to cause harm.

 

[MeSci]

I tagged you in this message, @Jonathan Edwards, but maybe you missed it?

(I realise you are in a lot of demand!)

 

[MeSci]

You know. The immune modulator. You must be very brainfogged today not to remember that.

Sorry, I don't know which immune modulator you are talking about.

 

[lansbergen]

Sorry, I don't know which immune modulator you are talking about.

Levamisole

 

[lansbergen]

It must be the nicotinic side for me. I was a very content ex-smoker for a number of years before ME/CFS hit.

I smoke like a chimmey. I always said I need both the PAM and the nicotine. Seems I was right.

Tiis morning I found at . http://papke.med.ufl.edu/reprints/pamreview.pdf

If PAM therapy is going to work, obviously the endogenous agonist must be present in sufficient concentrations and able to evoke responses that the allosteric modulator can potentiate.

Nicotine is a better agonist than acetylcholine.

 

[Sidereal]

Regarding steroids & ME, a double-edged sword for sure. I found some symptoms were reduced (pain and low blood volume/orthostatic intolerance in my case) but the overall result was a prolonged crash from a four-week course of high dose prednisone. It certainly forces some energy production in the short-term as you would expect but I don't believe this is a good thing in a situation like ME where oxidative stress is sky high and the reduced energy production may serve a protective purpose. On the steroid I went from mostly bedridden to being able to go for a 20-25 min walk a couple of times a week but the energy was totally fake and the side-effects were severe and unacceptable especially given that I was still severely disabled. The marginal benefits just weren't worth making a pact with the devil, though I suppose if one day I get into a situation where my UCTD progresses to organ-threatening lupus I'll have to reassess the situation.

 

[Jonathan Edwards]

Perhaps the autoimmunity can develop further down the line, e.g. due to a fall in endogenous cortisol production. If the HPA axis is infected, due to the initial low immune activity, then this could cause the drop in cortisol production, I think. (If my brain is functioning moderately well - it's a bit tired from wading through some scientific papers!)

So:

1. Low immune activity due to corticosteroids, stress and/or overexertion
2. Infection, whilst immune activity is still low.
3. Infection gets into brainstem.
4. Endogenous cortisol production falls.
5. Autoimmunity develops due to low cortisol.

Something like that. (Does that make sense, @Jonathan Edwards?)

Sounds a bit far fetched to me MeSci. I cannot see why a low cortisol would lead to autoimmunity to be honest.

 

[A.B.]

Sounds a bit far fetched to me MeSci. I cannot see why a low cortisol would lead to autoimmunity to be honest.

I've been wondering how the downregulated HPA axis and GI problems, both common in ME/CFS, fit into an autoimmune explanation. Are these things common in autoimmune disorders?

 

[Jonathan Edwards]

I've been wondering how the downregulated HPA axis and GI problems, both common in ME/CFS, fit into an autoimmune explanation. Are these things common in autoimmune disorders?

I do not think there is any evidence for low HPA activity being a causal factor for autoimmunity. It only shows up as Addison's diseases as far as I know. That may be associated with other autoimmune disorders but I do not think there is evidence that one causes the other. Each autoimmune disease targets a different organ. The gut does not seem to be that much affected, other than antibodies to parietal cells in pernicious anaemia. Inflammatory owel disease shows a hint of autoimmunity in some cases but seems largely to be an 'autoinflammatory' situation without clear evidence of T or B cell reaction against self.

 

[Kati]

Inflammatory bowel disease shows a hint of autoimmunity in some cases but seems largely to be an 'autoinflammatory' situation without clear evidence of T or B cell reaction against self.

Ahhhh... Interesting @Jonathan Edwards, I would love to hear more on your take on autoimmunity vs auto-inflammatory. What are the differences? Is auto-inflammatory being currently recognized in the medical world?

 

[WillowJ]

Steroids are a bit like Mephistopheles - you pay the price of selling your body to the devil in the long term in many situations. It is very hard to judge which situations short courses of steroids are justified for. There certainly are some but it is not so much a matter of logic as careful monitoring. In the 1960s a lot of children had a lot of steroids for asthma until they found that the survival rate was actually worse. But short courses of high dose steroid for temporal arteritis can prevent blindness. My impression is that although ME crash symptoms may sometimes respond to steroid that may not always be true by any means.

Thank you; that helps.

 

[WillowJ]

I thought low cortisol was related to chronic illness in general, and I don't think of it being important in ME particularly.

 

[Kati]

I thought low cortisol was related to chronic illness in general, and I don't think of it being important in ME particularly.

this is when system biologists come into play, especially when complex illnesses like ours are involved.
I don't think we can single out any symotom/ lab value and try to fix it. i think that system biology like the work of Gordon Broderick for instance can help tremendously in finding the upstream issue that we have. We need to go upstream.

 

[WillowJ]

this is when system biologists come into play, especially when complex illnesses like ours are involved.
I don't think we can single out any symotom/ lab value and try to fix it. i think that system biology like the work of Gordon Broderick for instance can help tremendously in finding the upstream issue that we have. We need to go upstream.

I agree with that in part (as far as cortisol, NKCC, etc. go), but would except the ones that have meaning generally, like low Vitamin D, or low potassium. Correcting such things can relieve some symptoms and avoid potentially dangerous situations, and is just basic medicine as far as I know. I've never had a doc of the paying-attention kind who didn't notice and treat these things (though the hostile kind would usually ignore everything).

And of course comorbid conditions like OI, migraines, etc. have established treatments and people should have access to those treatments.

However if people--knowing they are using experimental medicine--want to try various experimental things, as long as they are making their own choices and doing some research and being followed by a doctor (I know some here disagree because of the lack of availability of non-hostile doctors, but I really do think this is important, in case of bad side effects, and for legal reasons in parts of the US and wherever else it's not ok to Rx for yourself), I don't think we can disagree with this kind of choice (and I think, given the lack of potential treatments [as opposed to tinkering around the edges of symptoms], insurance should support it, i.e. pay).

Real science is a long time coming, and some of us are or have been in worsening patterns, and some are now older, where it might make sense to some--though not to others, which is also fine--to try something with an unknown risk:benefit ratio, or even one suspected to be high-risk/ high-benefit (someone once told me they might like to try bone marrow transplant, which at the time [has since improved] had an odds rate of something like 1 death: 7 complete cures, in MS.... I am not ready to try that, but I understand how someone would be).

 

[Kati]

Hi @WillowJ indeed individuals have every rights to use whatever therapy they wish, from over the counter to a therapy they have agreed with their treating physicians.

However i would be careful with claims of ME causing low vitamin D- are we very sure it is a direct link, measured and compared with patients with other chronic illnesses and healthy controls? could it be that patients with ME are more likely to have less sun exposure and low consumption Vitamin D fortified milk due to allergies?

Low potassium, my opinion is that it could be due to diarrhea or imbalances caused by different supplements including the so-called methylation protocol which can cause hypokaliemia. This would be different than saying that all ME patients have hypokaliemia, because it's not true. And in regards to B-12, some have elevated. b-12 levels. others' are low.

We need to be careful in calling what is the cause of vitamins and mineral imbalances. We are in desperate need of sound science, proper research with well defined patient population.

As a last note, I was once a bone marrow transplant nurse. We did autologus bone marrow transplants for some lymphomas and for mutiple myeloma. The mortality for autologus was much lower than the allogenic (unrelated donor) transplant, but still certainly not a procedure to be taken lightly.

 

[WillowJ]

hi, @Kati , I didn't mean to say (and don't think I said) we know ME causes these things. Just that they can have them and shouldn't be ignored. A lot of docs will ignore any finding in a CFS or complaining-of-"fatigue"/similar-with-no-"major medical"-diagnosis patient, whether or not it seems to be related to (or potentially exclusionary for) ME/CFS.

Low Vit D is prevalent in the population in general, particularly in the northern latitudes, but seems more common in chronically ill people, like MS and ME. Seems no one has figured out whether there is a relevance to the diseases themselves, except that they think sending TB patients to the country from London before the days of antibiotics, might have helped cure the TB for some patients due to sunshine/Vit D exposure (as London was very smoggy then). But can't find a benefit from Vitamin D supplementation (or moving south, IIRC) for MS (they looked).

I had low K+ before I ever knew what disease I had or was using any medicines/supplements (I now use some Rx which can deplete K+, which can't help), and at a time when diarrhea was not a significant problem, but my mom tends to have low K+, too. However, the reasons like this that you mentioned are sound ones to look for causes of metabolite problems.

While I had an ME doc tell me low K+ is prevalent among his patients, and I think there is some limited research indicating some metabolic reasons to suspect why this might be (I forgot the specifics, something about ion channels maybe), at this point we have more guesses about ME than answers. We would need well-powered studies controlling for variable such as those you mentioned, before we could make any kind of definite statement. And you're right, we don't have that.

My point about bone marrow transplant is just that people have different risk tolerance levels based on their personal circumstances. I did not in any way imply it was a light decision.

Again, I think we pretty much agree.

best wishes.