Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans

[Sly Saint]

Brain, Behavior, and Immunity
Volume 83, January 2020, Pages 309-314

Highlights
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We used pooled data to examine the dynamic of the fatigue response to inflammation.

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Sleepiness was also assessed as it is a symptom distinct from fatigue.

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The development of fatigue and sleepiness paralleled the cytokine response.

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A stronger cytokine response was related to developing more fatigue and sleepiness.

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There was no moderation effect of baseline inflammatory status.

Abstract
Inflammation is believed to be a central mechanism in the pathophysiology of fatigue. While it is likely that dynamic of the fatigue response after an immune challenge relates to the corresponding cytokine release, this lacks evidence.

Although both fatigue and sleepiness are strong signals to rest, they constitute distinct symptoms which are not necessarily associated, and sleepiness in relation to inflammation has been rarely investigated.

Here, we have assessed the effect of an experimental immune challenge (administration of lipopolysaccharide, LPS) on the development of both fatigue and sleepiness, and the associations between increases in cytokine concentrations, fatigue and sleepiness, in healthy volunteers. In addition, because chronic-low grade inflammation may represent a risk factor for fatigue, we tested whether higher baseline levels of inflammation result in a more pronounced development of cytokine-induced fatigue and sleepiness.

Data from four experimental studies was combined, giving a total of 120 subjects (LPS N = 79, 18 (23%) women; Placebo N = 69, 12 (17%) women). Administration of LPS resulted in a stronger increase in fatigue and sleepiness compared to the placebo condition, and the development of both fatigue and sleepiness closely paralleled the cytokine responses. Individuals with stronger increases in cytokine concentrations after LPS administration also suffered more from fatigue and sleepiness (N = 75), independent of gender. However, there was no support for the hypothesis that higher baseline inflammatory markers moderated the responses in fatigue or sleepiness after an inflammatory challenge.

The results demonstrate a tight connection between the acute inflammatory response and development of both fatigue and sleepiness, and motivates further investigation of the involvement of inflammation in the pathophysiology of central fatigue.

https://www.sciencedirect.com/science/article/pii/S0889159119304507?dgcid=author

 

[borko2100]

Sleepiness is a big problem for me. Sometimes I wonder if I have idiopathic hypersomnia or narcolepsy in addition to ME/CFS or if it's just another ME/CFS symptom.

I think it's the latter, because the symptom profile of those diseases doesn't fit me that well. Furthermore I have experienced periods of remission from the sleepiness symptoms. Rarely I would get sleepiness-free days, sometimes when I have a cold, they also disappear.

Who knows, maybe there's a difference in how people perceive fatigue. Some get sleepy, while others just want to lay down and rest.

 

[Peter T]

Below is more random thoughts triggered by the idea behind the study in relation to my ME than a comment on the above study itself.

Though I can suffer fatigue without sleepiness, indeed in general fatigue and insomnia go hand in hand, this is my more normal state, I don’t think I experience sleepiness without fatigue.

I do get periods of hypersomnia, usually at times of major relapses in my underlying ME. At such times I seem to need to sleep from sixteen up to twenty hours a day. This is also accompanied by fatigue, but is less common perhaps only occurring with my initial onset and then maybe irregularly on average every five or so years in the subsequent three decades. I am not sure how this might relate to the above study, but superficially at least it bears some similarities to the tiredness linked to acute CVAs or the acute phases in relapsing or remitting MS, or the need to sleep during an acute infection.

Having said that I do sometimes have PEM episodes, more minor crashes, that are associated with struggling to stay awake, but this is a much less common profile of PEM for me and I am not sure what the triggers or patterns of this are.

I wonder if there are two variables, what I call my ‘underlying’ ME that varies on a cycle of years in which low points are definitely associated with both sleepiness and fatigue, and my day to day week to week variation which relates to how I function within the current limits of my underlying ME. In general these shorter term crashes or PEM are associated with fatigue not sleepiness. Having said that these two variables are not independent, the worse my underlying ME the lower the trigger for short term PEM, also the more I over do it, the more frequently PEM is triggered the worse my underlying ME may become.

A related point is that frequently sleep does not reduce fatigue. It is very rare for me to have a good night’s sleep and to wake refreshed. It is much more common for me to experience unrefreshing sleep, that is to wake feeling more fatigued than before going to sleep. In such situations I may need to rest several hours lying down before considering any activity, before my brain fog is lifted. On a daily basis bringing the milk in and giving the cat breakfast (includes crushing half a tablet and adding six drops of another medication) are amongst the hardest things I have to do. Not because of the inherent difficulties in the tasks but because they have to be done before I have recovered from being asleep.

 

[Mij]

Furthermore I have experienced periods of remission from the sleepiness symptoms. Rarely I would get sleepiness-free days, sometimes when I have a cold, they also disappear.

I don't think we should read into this too much? In almost 30 yrs of illness I've cycled from hypersomnia, insomnia and normal sleep.

. . . and lying down to rest when I'm in PEM.

 

[Kitty]

It is interesting to try and tie down these definitions. I think my own experience is something like this:

Sleepiness (daytime)
Associated mostly with non-ME illness such as a virus, or tiredness after insomnia

Fatigue
Associated mostly with strong wakefulness

Fatigue plus immune symptoms (PEM)
Associated mostly with insomnia

Hypersomnia
Associated mostly with active ME flare

 

[erin]

I have to sleep 10 hours at night, if less I'm no good next day at all. 12 hours better. But that's half of the day's gone. Most of the time I don't even get up feeling refreshed after 10 hours.