Mar 4 2010 Severity of symptom flare after moderate exercise is linked to cytokine

Frank

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Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome.

White AT, Light AR, Hughen RW, Bateman L, Martins TB, Hill HR, Light KC.

Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah, USA.

Abstract Chronic fatigue syndrome (CFS) patients often report symptom flare (SF) for >24 h after moderate exercise (post-ex). We hypothesized that SF is linked to increases in circulating cytokines and CD40 Ligand (CD40L). In 19 CFS patients and 17 controls, mental and physical fatigue and pain symptom ratings were obtained together with serum for 11 cytokines and CD40L before and at 0.5, 8, 24, and 48 h post-ex. Before exercise, CFS had lower CD40L (p<.05) but similar cytokines versus controls. In subgroups based on SF at 48 h, high SF patients (n=11) increased in IL-1beta, IL-12, IL-6, IL-8, IL-10, and IL-13 (p<.05) 8 h post-ex. Low SF patients (n=8) showed post-ex decreases in IL-10, IL-13, and CD40L, and controls decreased in IL-10, CD40L, and TNFalpha (p<.05). Thus, in CFS, cytokine activity may vary directly with SF, which may explain prior inconsistent findings.

http://www.ncbi.nlm.nih.gov/pubmed/20230500
 

BEG

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Hi Frank, Very interesting post. Thanks for bringing it to our attention. My SF (symptom flare) occurs 48 hours after I've increased activity. I know that Post-Exertional Fatigue can occur 24-48 hours after activity per the guidelines on this disease. However, I've never encountered anyone with a 48 hour PEM. (Hope I used PEM correctly.) As an example, my granddaughter (brown-eyes) spent the night over the week-end. She went home Sunday. I was flat out yesterday. My legs could hardly hold me up. How does it work with you and others?.

B.E. Girl
 
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Robin

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Thanks, Frank! I love that the Lights are studying PEM. I wish someone would tank the PACE trial and take all that money and replicate this study on a larger patient sample.
 

HowToEscape?

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Hi Frank, Very interesting post. Thanks for bringing it to our attention. My SF (symptom flare) occurs 48 hours after I've increased activity. I know that Post-Exertional Fatigue can occur 24-48 hours after activity per the guidelines on this disease. However, I've never encountered anyone with a 48 hour PEM. (Hope I used PEM correctly.) As an example, my granddaughter (brown-eyes) spent the night over the week-end. She went home Sunday. I was flat out yesterday. My legs could hardly hold me up. How does it work with you and others?.

B.E. Girl
By SF do you mean the same crash as PEM?
I find that I often have a crash about 2 days after too much activity. I also have a (usually milder) flattening about 1 hour after exercise.
Or do you mean 2 different things by SF and PEM?
 

Hope123

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Hi Frank, Very interesting post. Thanks for bringing it to our attention. My SF (symptom flare) occurs 48 hours after I've increased activity. I know that Post-Exertional Fatigue can occur 24-48 hours after activity per the guidelines on this disease. However, I've never encountered anyone with a 48 hour PEM. (Hope I used PEM correctly.) As an example, my granddaughter (brown-eyes) spent the night over the week-end. She went home Sunday. I was flat out yesterday. My legs could hardly hold me up. How does it work with you and others?.

B.E. Girl
Just a mild correction here as I've noted the same problem elsewhere. The time used for definition of PEM is that it LASTS more than 24 hours; there is no specification on the time it occurs as it varies depending on the person. Some have it within hours; others after a few days - that's why it's hard to figure out for some of us which activities caused PEM. The lasting part is put in to distinguish it from people who have fatigue but which mostly go away with rest after 24 hours. -- e.g. how it was before CFS when I used to resume running after some time off.

Also, the articles' subjects - 70% had FM and CFS so if you just have CFS, like me, I'm not sure how applicable it is yet.
 

BEG

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By SF do you mean the same crash as PEM? I find that I often have a crash about 2 days after too much activity. I also have a (usually milder) flattening about 1 hour after exercise. Or do you mean 2 different things by SF and PEM?
l

Yes, I use SF and PEM interchangeably. I, too, have that "flattening" maybe 1-2 hours after over exertiing, which I atrribute to O.I. and low VO2 MAX. I simply don't have the capacity to sustain exertion. But with an hour of lying down, I've got the energy to do more. I'm OK with resting between activity the next day. However, 2 days after I've gone out of my energy envelop, so to speak, I can't get out of bed. How long that lasts depends on how long I pushed myself 2 days before. With a lengthy PEM, I would call it a relapse. A specialist told me that a relapse can last days or years.
 

parvofighter

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Cytokines... symptom flare... and TREATMENT example!

First, thanks to Frank for starting this thread. This cytokine storm after exercise jives beautifully with:

  • What patients have been saying about post-exertional malaise for decades; and
  • With what Kerr found when he treated chronic Parvovirus B19/CFS patients with IV immunoglobulins.
I'm having difficulty sleeping - and inserting the pdf of Kerr's Figure 2, & altho it says it's "attached" I won't know until this is posted... So let me try to describe it. Basically, Kerr did a pre/post measure in patients who had chronic parvovirus B19, with chronic fatigue, and raised IL-6, TNF-a, IFN-g, and macrophage chemoattractant protein (MCP-1). Gave them intravenous immunoglobulins (IVIg), and watched their serum cytokines tumble to zero in the months after IVIg. Exactly how I felt after my first high-dose IVIg infusions. Unfortunately I've had to keep going back to the trough - which would certainly fit with a retroviral model - constantly resurrecting the PVB19...

You can access the original Figs 1-3 of this paper at: http://www.cfids-cab.org/cfs-inform/Virus/kerr.etal03.pdf

A picture tells a thousand words....:Retro smile:

And it's another illustration of why I remain deeply concerned about CBT/GET for any patient who is experiencing these cytokine abnormalities.
 

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Dolphin

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First, thanks to Frank for starting this thread. This cytokine storm after exercise jives beautifully with:

  • What patients have been saying about post-exertional malaise for decades; and
  • With what Kerr found when he treated chronic Parvovirus B19/CFS patients with IV immunoglobulins.
I'm having difficulty sleeping - and inserting the pdf of Kerr's Figure 2, & altho it says it's "attached" I won't know until this is posted... So let me try to describe it. Basically, Kerr did a pre/post measure in patients who had chronic parvovirus B19, with chronic fatigue, and raised IL-6, TNF-a, IFN-g, and macrophage chemoattractant protein (MCP-1). Gave them intravenous immunoglobulins (IVIg), and watched their serum cytokines tumble to zero in the months after IVIg. Exactly how I felt after my first high-dose IVIg infusions. Unfortunately I've had to keep going back to the trough - which would certainly fit with a retroviral model - constantly resurrecting the PVB19...

You can access the original Figs 1-3 of this paper at: http://www.cfids-cab.org/cfs-inform/Virus/kerr.etal03.pdf

A picture tells a thousand words....:Retro smile:

And it's another illustration of why I remain deeply concerned about CBT/GET for any patient who is experiencing these cytokine abnormalities.
Thanks Parvofighter.

Lots of proponents of GET such as Peter White claim the symptoms ME/CFS patients feel when we exercise are just normal symptoms but we have forgotten what the normal symptoms associated with exercise are like, are wimps and cant cope with a little normal discomfort, etc. Evidence that what patients experience is abnormal is useful.
 

citybug

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Would this discount the ATP/mitchondria theory? Or could cytokines start because run out of ATP? I don't know which way to go unless they measure both in a study. It feels like running out of ATP, hitting the wall. Body could start cytokines to keep you in bed. Often second day after exertion I can do something, think I'm okay, then total crash, lasting several days (or months, function one a day week). If it were cytokines without ATP exhaustion couldn't we take advil and get up?
 

Dolphin

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Would this discount the ATP/mitchondria theory? Or could cytokines start because run out of ATP? I don't know which way to go unless they measure both in a study. It feels like running out of ATP, hitting the wall. Body could start cytokines to keep you in bed. Often second day after exertion I can do something, think I'm okay, then total crash, lasting several days (or months, function one a day week). If it were cytokines without ATP exhaustion couldn't we take advil and get up?
Just looked at article and no mention of mitochondria one way or another. In my head, it doesn't discount the theory but I don't really understand biochemistry, etc.
 

Hope123

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My bias from my reading is that it's more a cytokine issue than a mitochondria issue although there may be subsets of CFS that are mitochondrial illnesses and I don't know yet how cytokines affect mitochondria. My reasoning is that so far, of the people who have recovered with treament and who are well-documented in the literature, whether with antivirals, IVIG, or immunomodulators like rituximab, they have been able to recover without muscle symptoms reported to be an issue. These therapies modify cytokines either directly by getting at the cause (e.g. viruses) or by quelling the immune response, not by affecting mito as far as I know.
 

jeffrez

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I just typed an entire response and it got lost when I tried posting it. Too tired to write it all again - I'm in the midst of a crash right now, since day b4 yesterday. Just wanted to say that in my experience and opinion, PEM has most to do with the cell energy defects. Maybe increased cytokines are a byproduct or effect of that in some way - who can really tell with this crazy disorder - but I have had crashes even before I had much of an immune involvement, and this feels very much the same.

When I developed immune involved CFS, that fatigue was different, seemingly even non-overlapping. But there is no doubt that my stamina and endurance is decreased after the immune involvement, leading to crashes like I'm in now that before I wouldn't have had with that level of activity. So perhaps there is in fact some other interplay going on and it's not exclusively one or the other.

On the other hand, another thing I happen to think of is Dr. Cheney's reports that the immune systems of people w/CFS who have gotten stem cell therapy have been 100 percent normalized, while not all of them are recovered 100%. Or said another way, and perhaps more accurately, they are not recovered yet even though their immune systems appear to be. So to me that indicates that it has more to do with the cell energy defects, but it's really hard to speculate with any degree of certainty. That's just the way it seems to me personally, based on my own experience and data like Cheney reports.
 
K

_Kim_

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Welcome to the forums Mr. Kite

You've now been initiated into the frustrating and flawed world of vBulletin forum software. Thank you for taking the time to rewrite your post. In the future, should this (likely) happen again, the BACK button may bring you to your lost post. The [Preview Post] button also will store a copy of the post in your cache and some of us click it just for safe measure.

It is likely that PEM is likely related to cell energy defects (mitochondria?) and that, perhaps, exacerbates immune dysfunction. I'm in PEM mode right now - my initial symptoms post exertion were utter exhaustion, clouded thinking, and muscle twitching and soreness. After 24 hours, I can add sneezing, sore throat, and swollen lymph nodes to the list.
 

mermaid

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I was chatting with a friend today (who doesn't have ME/CFS) describing the fact that I have a lot of muscle pain this week and she was trying to persuade me that these aches and pains are just normal for my age (we are both 57). She says she has pain in her fingers and in an area of injury on her lower back, and I said that this is not the same thing - this is arthritis pain. However it did start me wondering about this whole area of pain and stiffness in old age as it is as you age that your mitochondria get increasingly knackered (sorry not a scientist so using layman's terms here). Not sure whether the cytokines fit in with arthritis too.

Anyway my own experience re the pain is interesting. I had the mito test done last September and came out with a very poor result. However at that point although I had many other symptoms of ME/CFS pain was not top of the list - only had it rarely.

In January I had whooping cough and was very ill and have been trying to recover from it since. My energy levels went way down and have just started to pick up in the last few weeks (ie not so much PEM if I am right in thinking this stands for Post Exertional Malaise?). Now I am getting pain after even the smallest bit of exercise that I did not get before. I have been doing some walking for over a month now, but the pain level is increasing. I am just curious (and not a little troubled) to know why this has suddenly triggered when I did not get it before.

Is it cytokine activity or more deterioration of the mitos following the whooping cough virus - or both?
 

wciarci

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Link to study on cytokine affects on mimitin in mitochondria. http://www.biomedcentral.com/1471-2121/10/23

From what I gathered, cytokines affect mitochondria esp ATP production, increase this protein called mimitin which then affects cell apopsis (sp?) . Sorry for the spelling I have crashed big time. Raked leaves off of a very small perenial bed on Sunday, resting alot in between but started to crash Wednesday, full crash yesterday and today. Darn it!

Wendy
 
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the link between inflammatory cytokine activity and mitochondrial disfunction was discussed in David Bell's 2007 (the title of which is far too long for me type!). Bell argues that infections induce the production of nitric oxide, which then, via a complicated process that I don't recall, disrupts mitochondrial activity.
 

free at last

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Thanks Parvofighter.

Lots of proponents of GET such as Peter White claim the symptoms ME/CFS patients feel when we exercise are just normal symptoms but we have forgotten what the normal symptoms associated with exercise are like, are “wimps” and can’t cope with a little normal discomfort, etc. Evidence that what patients experience is abnormal is useful.
Well i think White and hes merry men are wrong about that assumption, as i found relapses would sometimes occur with the same amount of excercise as times when they did not, Guess they would say im being selectively somatic to the same amounts of exercise. Now why the hell would i do that, one knows when we feel different, were not thinking we feel different sometimes and not others, with the same amount of excercise fatigue, just ridiculouse

I suppose in my early days when i had all the fevers, i was also selectively giving myself fevers, Funny that because when the fevers stopped but the illnes did not. I suppose i was selectively not giving myself fevers anymore too. Amazing what tricks the mind can play mr white just amazing. Idiots

if you ask me they have no ears, as they clearly dont hear storys like this very well, i said fevers mr white, sorry neil what psychosis, no fevers mr white, sorry i cant hear you psychosis Neil, Yeah what ever mr white. idiots
 

biophile

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Some biopsychosocialists appear to claim that post-exertional malaise and/or symptom exacerbation is just the normal "delayed-onset muscle soreness" that healthy people get. In my experience, these two are not the same. Others may claim that physical exertion causes symptoms because the system is already over-taxed from chronic psychological stress, which IMO is more interesting than the "abnormal beliefs" angle but sort of funny considering how exercise is touted as an effective treatment for stress.
 

Mithriel

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I have bad days three days after activity. I waken up more achy and feeling worse than usual think back and sure enough three days ago I did a bit extra. It doesn't happen because I expect it either - three days is longer than my memory:Retro smile: In ME it has always been said that malaise doesn't necessarily start until more than twenty four hours after activity.

This is different from what happens when I over do it

I have been ill so long I have no concept of normal and I can't explain what happens to me easily.

Mithriel