[special post] how may sleep affect TSW symptoms

this week i’m reading a paper on the relationship between sleep and skin inflammation. this paper investigates the effect of sleep loss on the inflammatory markers in our body. next week i’ll share a paper on the effect of inflammation on sleep!

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Sleep Loss and Cytokines Levels in an Experimental Model of Psoriasis

Camila Hirotsu, Mariana Rydlewski, Mariana Silva Arau´ jo, Sergio Tufik, Monica Levy Andersen

Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil, Departamento de Bioquı´mica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

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In summary:

This paper explored the effects of paradoxical (also known as the rapid eye movement sleep) sleep loss on the cytokines levels and how it affects psoriasis. They did experiments on mice, induced psoriasis behaviours in them and deprived them of sleep (ok, it’s all in the name of science.. T.T). The study measured cytokine and stress-related hormone levels, and found that sleep deprivation increased kallikrein (think of them as scissors that severe the glue between skin cells, they help in the shedding of dead skin cells) activities in the skin of psoriatic groups. Sleep deprivation plays an important role in the exacerbation of psoriasis through the modulation of the immune system in the epidermal barrier.

In case you didn’t read last week’s post on depression and have no idea of the scientific terms I used, I’ll introduce you to them again J cytokines are the messengers of the immune system. Broadly classified into two classes: pro-inflammatory (type 1) and anti-inflammatory (type 2). I guess the meaning is obvious in its name. We’ll focus on the pro-inflammatory cytokines today, namely IL-1 and IL-6. IL stands for interleukin by the way, in case you’re curious.

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Point 1______________________________________

Legend:

SHAM+CTRL: Normal mice and normal sleep
SHAM+PSD: Normal mice and paradoxical sleep deprived for 48 hours
PSO+CTRL: Psoriatic mice and normal sleep
PSO+PSD: Psoriatic mice and paradoxical sleep deprived for 48 hours
PSO+SR48: Psoriatic and sleep deprived mice gets 48 hours of undisturbed sleep (called a sleep rebound).


Image taken from the paper. A) IL-1 beta levels, B) IL-6 levels, D) IL-10 levels. The coloured lines are added by me to indication increments/reduction between the different groups. Pink/red is for normal mice, while blue/green is for psoriatic mice.

I want to highlight the difference of both the IL-1 and IL-6 levels between PSO+CTRL and PSO+PSD. Compare the length of the blue line to the length of the pink line. This denotes the difference between the normal mice group and the psoriatic mice group – even though their pro-inflammatory cytokines also increased after sleep deprivation, the magnitude is not as huge as psoriatic mice. In other words, the increment in inflammatory cells are much larger in psoriatic mice.

Also, the increment of IL-6 is almost twice that of IL-1.

After sleep rebound, the levels of pro-inflammatory cytokines reduce, but it’s still higher than mice that got normal sleep.

IL-10 is an anti-inflammatory cytokine. The amount in the mice’s blood dropped after being sleep deprived, but after sleeping, it rose even higher than before! For the normal mice, sleep deprivation caused the IL-10 levels to drop to a level that is similar to that of psoriatic mice who have also been sleep deprived.

What does all this mean?

1. Not all are created equal, that’s all I can say. I have a friend who had pretty bad acne. He drinks and clubs but doesn’t smoke. He has a friend who smokes and drinks and sleeps late but has perfect skin. Life is not fair. Psoriatic mice will produce more pro-inflammatory cells when put through the same treatment as normal mice, even though their anti-inflammatory cells drops to similar levels.

2. You can pay off your sleep debt, but it’ll take way longer than the duration you stayed up for to completely pay it off, at least this is what the cytokine profile says.

3. Being deprived of sleep WILL exacerbate inflammation, even though getting enough sleep doesn’t mean it’ll decrease inflammation, but at least you’re not feeding oil to the fire.

4. Even though the anti-inflammatory cytokine is bumped up after the sleep debt is paid, it’s not a valid reason for one to stay up thinking that “the increase in the anti-inflammatory cytokines will have an anti-inflammatory effect on me!”. If you add all the cytokines together, giving a negative value to pro-inflammatory cytokines and a positive value to anti-inflammatory cytokines, the overall value will be negative = HELLO INFLAMMATION.

K5 is one of the kallikrein investigated. The graph shows their activity across the different groups. Higher activity means that the scissors is busy cutting up pieces of our skin cells.

Why is this undesirable? In psoriasis, one of the problems on top of the inflammation is the excessive skin cell turn over. The skin cells are shedding off way too quickly, and the enzymes in charge of breaking down the inter-cellular glue are responsible for it.

So, after sleep deprivation the K5 is working overtime on a redbull overdose, cutting up more skin cells than it normally does. I think it’s only logical to expect more premature skin fall. But after replenishing sleep, the level falls, although it’s clearly still higher than normal mice. Again.. life is unfair. You can see that even if a normal mouse doesn’t sleep for 48 hours, its K5 activity is still lower than a psoriatic mouse which gets restful sleep.

Even though TSW is not psoriasis, by the symptoms are much alike, I would expect the molecular interactions and reactions to be very similar to what a psoriatic patient goes through. Thankfully, it’s only temporary for us. PHEW. My advice? Rest up so that you don’t worsen the symptoms.

In a nutshell:
Sleep deprivation increases inflammation in the body, and jacks up the enzyme that breaks down our skin. People with normal skin do not have as much inflammation, so they don’t exhibit said symptoms, but for us who are already having pretty damn much inflammation in our body, any slight increment will worsen the situation.

This is also the reason why I suggest taking medication to help get some sleep during the initial insomniac days (and nights) at the start of withdrawals, because I observed my skin getting much worse after not sleeping. The itch and dryness seem to quadruple in their intensity after a sleepless night. It’s not good.

Point 2______________________________________

Stress is a relevant factor in triggering psoriasis symptomatology and is intrinsically related to sleep deprivation through HPA activation.

This actually got me stumped for a bit. Doesn’t stress increase the cortisol level in our body, which are anti-inflammatory in nature? Why would stress lead to more inflammation then? Turns out.. our body adapts to stress. Under prolonged stress, the body no longer sense it as a fight or flight situation, cortisol level actually falls below normal, which would explain for promoting inflammation in the body. This is for normal people. Prolonged stress will encourage inflammation in the body.

For psoriatic people, their usual response to stress is lower cortisol level.  It just is that way for them.

Maybe, just maybe, if you stress a little less, it can help prevent the worsening of the symptoms that you’re experiencing in TSW. Assuming our body is more alike to a psoriatic patient during TSW, lesser stress would mean higher cortisol levels, which means lesser inflammation, right?

Point 3______________________________________

Our results also demonstrate a cause-effect relationship between the immune response and K5 activity, showing that the pro-inflammatory cytokines IL-2 and IL-12 explain 58% of the changes observed in K5 activity. These data suggest that  sleep deprivation may change the cytokine environment leading to excessive protease activity, which in turn affects the epidermal barrier and contributes to psoriasis pathogenesis.

The steps are broken down as follows:
1. Sleep deprivation
2. Increased inflammatory cytokines level
3. Increases K5 activity
4. Increased rate of skin fall
5. Decrease integrity of epidermal barrier
6. Increase chances of skin irritation, worsens psoriasis

Applying this to TSW, all the steps will be the same up till step 5. The step 6 for TSW would probably be more broken skin, more pain, more ooze. More itchy too, since everything will irritate the super sensitive skin.

Point 4______________________________________

Paradoxical Sleep deprivation has been demonstrated to increase type-1 cytokines IL-1 beta, IL-6 and IL-12 levels in rats in a sleep loss-dependent manner. Since our results show that these cytokines can modulate the K5 function, it is important to highlight the importance of good sleep quality for maintenance of skin integrity.

Lack of sleep itself has important effects on immunological integrity and nocturnal secretion of cytokines.

A gentle reminder: type-1 cytokines are pro-inflammatory cytokines.

I guess the saying “beauty sleep” is true. HAHAHA! Now it’s backed up with scientific evidence! Get quality sleep and skin will have lesser problems. Quality sleep means a normal amount of rapid eye movement sleep and deep sleep! It doesn’t mean that if you sleep for 12 hours a day, it’ll be better for you.

Point 5______________________________________

Many facets of inflammation such as pro-inflammatory cytokines present circadian pattern in humans, typically peaking during the night.

Ever wondered why you feel more itchy at night? This might be the reason.

Or it could be due to the fact that there’s no longer anything to distract me from the itch after I go to bed.

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so these are the more interesting points that i’ve noted down.
some of them actually answered some of my doubts in the past. i have personally experienced increased itching at night back then, but i just can’t seem to find the link. perhaps this was what happened in my body, although i won’t be surprised if there are more that’s actually happening in reality. but being able to have a vague idea or a possible explanation is better than having none at all.

one point i’d like to raise is, this experiment actually investigated the loss of paradoxical sleep, meaning they tried to eliminate the mice of REM sleep. for those of you who aren’t familiar with sleep, REM is like the lighter sleep stage before you enter the deep sleep stage. each serves a different purpose. at the end of the paper, they did state that it is more likely for humans to undergo acute sleep deprivation and/or chronic sleep restriction instead of paradoxical sleep deprivation, but this experiment mainly tries to show  the relationship between pro-inflammatory cytokines and the kallikrein protease that will affect the shedding rate of the skin. it doesn’t mean that we’ll have to rid ourselves of REM sleep to experience such a symptom, because there are many other reactions that will increase those pro-inflammatory cells in our body.

this paper merely opens a window to show us how pro-inflammatory cells will have an impact on our skin.

and now it’s my turn to get my beauty sleep!!!

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6 thoughts on “[special post] how may sleep affect TSW symptoms

    • HAHAHAHHA aww leslie, i think only you and a few others actually appreciate such sharings.
      thanks for the heads up!!
      it makes my sharing more worthwhile 🙂

  1. Hi Juliana!
    I was just googling some stuff and happened to bump into your blog. First of all, I think it’s a great idea to share your story just like you do. You are certainly helping other people, too. Besides, information is never too much. A curious fact is that I am one of the authors of this study. By the time we published it, I was getting my master’s degree and working with animal models of psoriasis, and came across this model. It’s really nice to see that this knowledge is being shared, and somehow, helping people to better understand. Thank you for sharing, congrats on your blog and keep up! 🙂
    Mariana

    • HI MARIANA!

      OH MY GOD, i can’t describe how surprised i am to know that you’re one of the authors! :O that’s me right now, i can’t close my jaw.

      thank you so much for leaving such an encouraging comment! you have no idea how your research will help shed more light on the complexity of the disease and all things related to inflammation.

      i hope i did not misinterpret your study in any way possible! 🙂

      thanks once again! your comment really took me by surprise, a very pleasant one!

      xoxo

  2. Pingback: [special post] how does inflammation affect sleep | juliana's topical steroid withdrawal journey

  3. Pingback: [special post] correlating sleep depth and inflammation | juliana's topical steroid withdrawal journey

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