[special post] how does inflammation affect sleep

this is part 2 of the sleep series. i’ve wrote about how sleep may possibly affect TSW symptoms a few weeks ago, today i share 2 papers that talk about how the immune system affects sleep.


The Role of Cytokines in Sleep Regulation

James M. Krueger*

Sleep and Performance Research Center, College of Veterinary Medicine, Washington State

University, Pullman, WA 99164-6520, USA


In summary:

this paper discusses the positive effects of interleukin-1 beta (IL1) and tumor necrosis factor alpha (TNF) (amongst the other sleep regulating substances) on non-rapid eye movement sleep during normal and inflammatory conditions. the mechanism of how they affect sleep is also proposed, but the author acknowledges that the entire mechanism responsible for sleep regulation may be beyond our current findings and understandings.


Point 1______________________________

Many of the variables that affect sleep have been linked to hormonal and humoral mechanisms. These mechanisms are often linked to each other in biochemical cascades and feedback loops and link sleep to multiple other physiological and mental processes. … The regulatory output is an emergent property of the entire system. … Similarly, sleep disorders occurring during pathologies likely result from the disproportionate stimulation of one or more of the humoral/hormonal mechanisms.

I have always seen our body as a complex machine that contains thousands of processes within. Each output is not merely a result from one single process, but rather, a combination of many. The inputs might not be singular too, which makes it even harder to pin point a certain factor which may affect the end result, in this case, it’s sleep.

Because everything works in harmony to give rise to the symptoms that we may observe, it’s quite futile to state how one variable alone will affect the state of the health. The body is a system, and everything is in a fine balance. Once you tip the balance, you get a weird symptom. Perhaps that’s also the reason why it’s harder than you think to maintain good health, because it is not on the extreme ends of the scale – It’s in the centre. Too much or too little of something isn’t good for you. And the notion of “moderation” is not that clear and distinct, and differs from person to person. Before we discover our personal “sweet spot”, we’d always be hovering above or below the optimum level, and that means a deviation from good health.


Point 2______________________________

However, it is not possible to isolate sleep as the independent variable because most, if not all, physiological parameters change with sleep. As a consequence, investigators have developed lists of criteria to be met before a substance is considered a sleep regulatory substance. Criteria common to these lists are:
a) The substance if injected should enhance sleep.
b) If inhibited, sleep should be reduced.
c) The level of the substance should vary in brain with sleep propensity.
d) The substance should act on sleep regulatory circuits.
e) The substance should be altered in pathological states associated with enhanced sleepiness.

All of these criteria have been met by IL1, TNF, growth hormone releasing hormone (GHRH), adenosine, and prostaglandin D2 for non-rapid eye movement sleep (NREMS) regulation.

For rapid eye movement sleep (REMS) regulation, prolactin, NO, and vasoactive intestinal polypeptide also meet these requirements.

The definition of a sleep regulatory substance (SRS) is mainly defined by the criteria set by investigators. I think it’s more than sufficient to understand just point a and b. The presence of SRS will enhance sleep, and the lack there of leads to reduced sleep.

Non-rapid eye movement sleep consist of 3 stages, and as the name suggest, there is no rapid eye movements. Stage 3 is the deepest of them all where your brain does most of the resting. rapid eye movement sleep is light sleep (where you have a lot of dreams). Remember that our body is a balance, so all the chemicals and cells named as SRS are in fact in a balance to give you a normal sleep cycle.

When they are not balanced, we get funky sleep. I know that there are some of you who gets insomnia (which is seemingly unrelated to today’s topic on sleep, but it’s still somewhat related to our body. Not sure if anyone is interested at all.), and there are some who sleeps too much and still feel tired, and it maybe just me who have too many dreams when I do fall asleep back then.


Point 3______________________________

Conditions that enhance endogenous production of IL1 or TNF, e.g., excessive food intake or infectious disease, promote NREMS.

So it seems like food coma goes beyond the common belief of “the stomach drawing blood away from the brain”. And this also gives me a hint of idea why there may be a link between itching and eating. Excessive food intake increases the IL1 production! And IL1 is a pro inflammatory cytokine, which means.. pronounced inflammatory actions such as itching and swelling.


Point 4______________________________

Both IL1 mRNA and TNF mRNA increase in the brain during sleep deprivation.

The messenger RNA (things that decrypt DNA into readable information by our cells to produce the respective proteins) of IL1 and TNF are increased during sleep deprivation. More messengers to pass the production notice, factory produces more inflammatory IL1 and TNF as a result. It points back to how lack of sleep will increase inflammatory responses.


Point 5______________________________

TNF is elevated in patients with chronic fatigue syndrome, chronic insomniac patients…

Why am I not surprised. I’m not sure which is the cause and effect though, since they sleep and TNF affects each other both ways. Chronic fatigue probably means not getting good sleep, the lack of sleep will raise pro-inflammatory cytokines. Nothing new here. Same goes for people who has insomnia.


Point 6______________________________

There are also several findings showing that cerebral blood flow during sleep is enhanced in those areas disproportionately stimulated during prior waking.

Totally unrelated to TSW and inflammation, but I find this interesting because there’s a phrase in Chinese that says 日有所思, 夜有所夢 (if you think about it in the day, you will dream about it at night), now it’s backed up by scientific evidence!


How (and why) the immune system makes us sleep

Luca Imeri and Mark R. Opp


In summary:

this paper investigates the possible mechanism that can explain for why the body makes us sleep more when it’s dealing with an infection. they attributed it to the immune signalling molecules are amplified during an infection.

DISCLAIMER: TSW is NOT an infection, but as i suspect that our body is highly inflammed during TSW, i thought it’s suitable to look at how the inflammation (irregardless of the cause) will affect sleep.


Point 1______________________________

Historically, it was widely thought that the only consequence of night time sleep loss was daytime sleepiness resulting in cognitive impairment.
We now have compelling evidence that, in addition to cognitive impairment, sleep loss is associated with a wide range of detrimental consequences, with tremendous public-health ramifications. For example, short periods of sleep loss at the time of vaccination reduce the vaccine’s effectiveness. Sleep loss is associated with increased obesity and with reduced levels of leptin and increased levels of ghrelin, the combination of which increases appetite. Sleep loss is also associated with diabetes and impaired glucose tolerance in a dose-related manner: individuals that report sleeping less than 6 h per night are ~1.7 times as likely, and those that report sleeping less than 5 h per night are ~2.5 times as likely, to have diabetes than individuals that obtain 7 h of sleep. Cardiovascular disease and hypertension are also associated with sleep loss: the risk of a fatal heart attack increases 45% in individuals who chronically sleep 5 h per night or less. Collectively, these examples demonstrate wide-ranging consequences of sleep loss on physical health. Obesity, diabetes and cardiovascular disease are pathologies that are characterized, in part, by inflammatory processes.

In summary, loss of sleep leads to more problems than we ever thought of, beyond feeling sleepy the next day, which will impair cognitive abilities. Long term sleep loss will increase your risk in getting obesity, diabetes, and cardiovascular diseases, which pretty much mean your metabolism system is out of whack, and you’re screwed. All in all, not getting sufficient sleep is equivalent to committing suicide slowly.


Point 2______________________________

IL-1 and TNF increase non-REM (NREM) sleep in several species (rat, mouse, monkey, cat, rabbit and sheep) irrespective of the route of administration. NREM sleep that follows the administration of IL-1 or TNF has some characteristics of physiological sleep in the sense that it remains episodic and is easily reversible when the animal is stimulated. However, IL-1 generally causes fragmentation of NREM sleep. The magnitude and duration of IL-1’s effects on NREM sleep depend on the dose and time of administration: very high doses are NREM-sleep suppressive and, in rodents, IL-1 is more effective in increasing NREM sleep when it is administered before the dark phase of the light-dark cycle.

There are two types of sleep, the lighter stages also called the REM sleep, and the deeper stages where most of our cell’s restorative work takes place, it’s generally categorized as non-REM sleep. REM sleep is categorized by the episodes of dreams that we usually get during that stage of sleep.

In the animals tested, it was found that administration of IL-1 and TNF, both pro-inflammatory substances will increases NREM sleep. However, IL-1 will break up the duration of NREM sleep, instead of an undisturbed cycle of NREM sleep, it is now fragmented.

The effects of IL-1 are dose and time dependent, high doses suppresses NREM sleep (meaning more REM sleep), and it is most effective in increasing NREM sleep when administered before the sun goes down.

So now we see, if we increase IL-1 slightly, it’ll induce more NREM sleep, but too much of it will end up suppressing it.


Point 3______________________________

In humans, IL-1 plasma levels are the highest at the onset of sleep.

Why do I itch more when I sleep? Is it because there’s nothing to distract me? Apparently.. it may be due to a surge in the pro-inflammatory cytokine. The “aha” moment.

Makes sense?


The rest of the second paper was rather irrelevant to my interest so I gave up trying to make notes for it.

I was interested in reading up on sleep and the immune system because I found some anomalies between me and a few of my skin friends.

While I know that everyone is different, but I still felt curious about what could possibly  be happening in their body that could explain for the discrepancies. Personally, I suffered from insomnia a hell lot during TSW, but this two skin friends of mine were the opposite. They slept around the clock whenever they flared. It’s something I didn’t experience even when I was flaring back then. I get very fragmented sleep, like 3 hours of sleep before waking up for 2 hours and diving back for a few more hours of sleep.

Honestly speaking, I still have no idea what accounted for the difference between me and them. It may be the gender, because another skin friend of mine (who’s female) had insomnia just like me.

These papers talked about how the cytokines will increase NREM sleep, but NREM sleep is different from total sleep time. I can sleep for 8 hours but spent 50% of my time in NREM, while a person undergoing severe inflammation spends 70% of the 8 hours in NREM. This is not equivalent to me sleeping for 8 hours and my friends sleeping for more than 10 hours.

Maybe.. there’s more to it. 😛 After all, IL-1 and TNF is NOT the only proinflammatory cytokines in our body, neither are they the ONLY substance that will affect our sleep. Whatever I just discussed right now only offers a slit for me to observe the bigger problem. And just as what the first point in the first paper said, the things that we can physically observe are the emergent property of the entire system. Clearly, I’m missing something.


9 thoughts on “[special post] how does inflammation affect sleep

  1. fascinating–i studied sleep a lot in high school and it really is the foundation to our health!! it’s important to prioritize it, especially during TSW. the only thing i dislike about waking up after a deep, restful night’s sleep is to skin that is…crusty and dry. it always looks the worst then. then it’s into the shower i go to quench things up.

    TSW seriously throws everything off. i’ve been waking up at 5-7PM every day. but at least with online classes it isn’t interfering with my studies TOO much 😛

    • :))) thanks for reading grant! entries like this usually put people to sleep. i’m surprised you read through it! hahaha was it because you couldn’t sleep?

      i remember dreading waking up because of the exact reason. that dryness is something i don’t enjoy at all. i wonder if thousand year old mummies feel that way when they came back to life in movies? however, i remember the skin looking the best right after i wake up, before the blood gets pumped throughout my body (so my skin looks less red and angry). but the dry skin.. that’s why i avoid the mirror at all cost. but it’s a different story now. HAHAHAH i have a mirror facing me as i type this reply to you. morning showers are always welcomed, if i can get over the initial burst of pain i get from my cracked skin touching the water.

      thank god for online classes! i wish i had them last time, but some of my classes were too small for the lecturer to record it and put it online. oh well. good luck!!!

      • you’re welcome–i’m a big science geek. i’ve always loved learning about sleep and skin, even before tsw. the inflammation article was interesting–answers my Q’s about why my skin looks like garbage on days where i get no sleep.

        poor little mice though, being sleep deprived. T_T at least their hard work is commemorated in places like this research lab in russia, where mice are used in genetic research. http://i.imgur.com/lFKK0xS.jpg ha!!

        it’s hard waking up. even though it’s crusty and scaly the skin color is still really neutral but there’s no way i’d brave through the day with dinosaur skin (good word). the heat from the water makes the patches red again and “wakes up” my red sleeve but at least the skin is nice and plump.

        here’s a visual for you to laugh at: i’ve developed some nasty cuts on my arm creases from scratching and it hurts to bend my arms. 😦 so i’ve been going about my days t-rexing it. i already have the dinosaur SKIN…now i got the arms. whats next? D:

        at least i don’t have harlqeuin ichthyosis :S basically tsw but forever.

      • hahaha thanks for your description, it was indeed funny to imagine it. i’ve been a t rex before too 😛 let’s hope you don’t end up extinct like the t rex, okay?

        the little statue of the mice is so cute! somewhere out there are people who count the sacrifices these little mice made. T.T makes me feel like tearing up.

        oh man, harlequin ichthyosis is scary. i feel bad for those peeps.. sigh.

  2. I took a class on circadian rhythm and there is a lot going on systemically via hormones to get us to sleep. It’s no wonder really that sleep is so hard to come by. Hell even those with no other health problems have hard time sleeping! I’ve been so lucky to be great at sleeping- even during withdrawal. I’m realizing now that it’s no small feat!

    • hello esther! it’s great that you’re sleeping well! and i totally agree with what you learnt, that there’re so much at play that can affect sleep, and sleep also affect so much functions in our body.. i think people need to give good rest more importance when considering overall health!

      it’s so cool that you learn about circadian rhythm in school! what’s your major!?

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