Here’s the #1 link on Google Scholar that comes up on a search for “inflammation sleep deprivation” (> 800 citations).
They’re looking at inflammatory cytokine levels (CRP, IL-6, and TNF-a), which I can confirm (biomedical engineering MS student currently studying immunology) are key drivers of the inflammatory response, though the immune system is a complex interconnected pathway without a straightforward protein “gas pedal.” Here’s my quick interpretation of the abstract in terms of the support it lends for the sleep deprivation/inflammation connection.
Pros:
n > 50,000, no evidence of publication bias
Found sleep disturbance (poor sleep, sleep complaints) associated with CRP and IL-6, and shorter sleep duration (< 7 hours/night) with CRP.
The researchers do note in the last sentence findings from another study that “Indeed, treatment of insomnia has been found to reduce inflammation and together with diet and physical activity represents a third component in the promotion of sleep health.” The insomnia treatments in the linked study were CBT and tai chi.
Cons:
Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFα.
Nothing at all was associated with TNF-a (which the researchers chalk up to “low statistical power” with n = 672, as opposed to the n=34,000 for CRP and n=3,000 for IL-6).
The biggest effects were for people with sleep disturbance and complaints, but one interpretation is that this is due to an underlying autoreactive or pathogenic immune response that causes poor sleep.
My takeaway from this study is that it actually lends strong support to the idea that inflammation is not driven by sleep deprivation. The right interpretation seems to be that if you’re having sleep disturbances, then your doctor may want to check for an inflammatory cause.
However, the authors themselves say in the discussion that “sleep disturbance is associated with inflammatory disease risk and all-cause mortality, possibly by effects of sleep disturbance on inflammatory mechanisms.”
The authors think that sleep deprivation enhances TLR-4-stimulated production of IL-6 and TNF-a. The immune pathway starting with TLR-4 is well-established, and you can find it covered in a good textbook like Janeway.
The key component of these authors’ argument, though, is linking sleep deprivation to that pathway. As evidence, they cite a 2006 study (n=30) that assessed IL-6 and TNF-a production with an experimental manipulation comparing levels after 8 hours of sleep vs. 4 hours of sleep. Then they took blood assays at 8 AM, 12 PM, 4 PM, 8 PM, and 11 PM. This study has a lot of problems:
“Data were analyzed using SAS statistical software (version 9.13; SAS Inc, Cary, NC). Missing values were handled using cell-wise deletion.” Missing data is a common problem in research, but there are sound statistical methods for dealing with it. Deleting the missing values is not one of them. And how the heck are these researchers missing data when they’re collecting it themselves?
“Compared with baseline levels, the percentage of monocytes expressing IL-6 and TNF-α was significantly increased at 8 AM after PSD (t107 = −2.3; P<.05); this increase normalized at subsequent time points.” So they found an increased percentage of monocytes expressing IL-6 and TNF-a at 8 AM, but not at 12 PM, 4 PM, 8 PM, or 11 PM. No mention of multiple comparison corrections in their analysis, but let’s hope they did it and didn’t tell us about it. Also, unlike their nonsignificant P-values, which are given precisely, they merely say “P < .05.” So then they went on to the exploratory analysis.
“The number of monocytes was not different at the 8 AM time point after PSD (t1,29 = −0.3; P>.85).”
Finding elevated monocyte cytokine expression at 8 AM, they also looked at transcription in these monocytes at only this timepoint, and found that indeed, mRNA is at 6-fold (IL-6) and 2-fold (TNF-a) levels.
All participants had their sleep deprivation on day 4, after 3 days sleeping in a lab having their blood drawn 5 times a day.
Let’s just say that this is not strong evidence of sleep deprivation-driven inflammation. But it is probably some evidence. This paper (but not the original metastudy) also links to 5 other papers buttressing its claim of a sleep deprivation-inflammation causal link.
I’m not going to go this in-depth into all of them, but let’s at least get the takeaways:
Elevated lymphocyte levels found both after sleep deprivation and in the afternoon and evening of the day following sleep. I have to admit I find the abstract confusing: they say that a decrease in monocytes, NK cells, and lymphocytes may “serve to support ongoing immune defense.” That’s the opposite of how I’d interpret a low level of white blood cells. But maybe I’m missing something.
Sleep deprivation reduces NK and cellular immune responses in humans. The title says it all.
The study finds impairment in vigilance after sleep deprivation to 6 hours of sleep/night, increases in IL-6 secretion and, in men but not women, TNF-a, as well as decreases in cortisol.
“Relative to the partial sleep deprivation condition, subjects in the total sleep deprivation condition had elevated plasma levels of sTNF-αRI on day 2 (P = .04), day 3 (P = .01), and across days 2 to 4 of sleep loss (P = .01) and elevated levels of IL-6 on day 4 (P = .04).”
“The CRP concentrations increased during both total (88 hours awake) and partial (4.2 hours of sleep) sleep deprivation conditions, but remained stable in the control condition.”
Note that in these studies, the researchers are commonly taking frequent blood samples. For example, in that last study, they took hourly blood samples. They’re being continuously monitored, catheterized, in a lab environment, sleeping with a catheter, and getting their rectal body temperature taken. Again, I think we have to worry about the potential confounding impact of stress, blood loss, etc on driving this immune response.
Looking at the results from these 5 studies, we see a mix of effects. In sleep deprivation, sometimes inflammatory cytokines are up, but other times, inflammatory cells are down. Results are there but inconsistent.
Moreover, and crucially, these are short-term studies that don’t investigate the health impacts we’d actually care about from inflammation. That’s not their fault—they’re a valuable contrbution to scientific knowledge—but we can only learn so much from studies like this. I am not ready to accept with any great confidence a claim that “sleep deprivation shreds your immune system” based on this data.
Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation (schi-hub link).
Here’s the #1 link on Google Scholar that comes up on a search for “inflammation sleep deprivation” (> 800 citations).
They’re looking at inflammatory cytokine levels (CRP, IL-6, and TNF-a), which I can confirm (biomedical engineering MS student currently studying immunology) are key drivers of the inflammatory response, though the immune system is a complex interconnected pathway without a straightforward protein “gas pedal.” Here’s my quick interpretation of the abstract in terms of the support it lends for the sleep deprivation/inflammation connection.
Pros:
n > 50,000, no evidence of publication bias
Found sleep disturbance (poor sleep, sleep complaints) associated with CRP and IL-6, and shorter sleep duration (< 7 hours/night) with CRP.
The researchers do note in the last sentence findings from another study that “Indeed, treatment of insomnia has been found to reduce inflammation and together with diet and physical activity represents a third component in the promotion of sleep health.” The insomnia treatments in the linked study were CBT and tai chi.
Cons:
Neither experimental sleep deprivation nor sleep restriction was associated with CRP, IL-6, or TNFα.
Nothing at all was associated with TNF-a (which the researchers chalk up to “low statistical power” with n = 672, as opposed to the n=34,000 for CRP and n=3,000 for IL-6).
The biggest effects were for people with sleep disturbance and complaints, but one interpretation is that this is due to an underlying autoreactive or pathogenic immune response that causes poor sleep.
My takeaway from this study is that it actually lends strong support to the idea that inflammation is not driven by sleep deprivation. The right interpretation seems to be that if you’re having sleep disturbances, then your doctor may want to check for an inflammatory cause.
However, the authors themselves say in the discussion that “sleep disturbance is associated with inflammatory disease risk and all-cause mortality, possibly by effects of sleep disturbance on inflammatory mechanisms.”
The authors think that sleep deprivation enhances TLR-4-stimulated production of IL-6 and TNF-a. The immune pathway starting with TLR-4 is well-established, and you can find it covered in a good textbook like Janeway.
The key component of these authors’ argument, though, is linking sleep deprivation to that pathway. As evidence, they cite a 2006 study (n=30) that assessed IL-6 and TNF-a production with an experimental manipulation comparing levels after 8 hours of sleep vs. 4 hours of sleep. Then they took blood assays at 8 AM, 12 PM, 4 PM, 8 PM, and 11 PM. This study has a lot of problems:
“Data were analyzed using SAS statistical software (version 9.13; SAS Inc, Cary, NC). Missing values were handled using cell-wise deletion.” Missing data is a common problem in research, but there are sound statistical methods for dealing with it. Deleting the missing values is not one of them. And how the heck are these researchers missing data when they’re collecting it themselves?
“Compared with baseline levels, the percentage of monocytes expressing IL-6 and TNF-α was significantly increased at 8 AM after PSD (t107 = −2.3; P<.05); this increase normalized at subsequent time points.” So they found an increased percentage of monocytes expressing IL-6 and TNF-a at 8 AM, but not at 12 PM, 4 PM, 8 PM, or 11 PM. No mention of multiple comparison corrections in their analysis, but let’s hope they did it and didn’t tell us about it. Also, unlike their nonsignificant P-values, which are given precisely, they merely say “P < .05.” So then they went on to the exploratory analysis.
“The number of monocytes was not different at the 8 AM time point after PSD (t1,29 = −0.3; P>.85).”
Finding elevated monocyte cytokine expression at 8 AM, they also looked at transcription in these monocytes at only this timepoint, and found that indeed, mRNA is at 6-fold (IL-6) and 2-fold (TNF-a) levels.
All participants had their sleep deprivation on day 4, after 3 days sleeping in a lab having their blood drawn 5 times a day.
Let’s just say that this is not strong evidence of sleep deprivation-driven inflammation. But it is probably some evidence. This paper (but not the original metastudy) also links to 5 other papers buttressing its claim of a sleep deprivation-inflammation causal link.
I’m not going to go this in-depth into all of them, but let’s at least get the takeaways:
Elevated lymphocyte levels found both after sleep deprivation and in the afternoon and evening of the day following sleep. I have to admit I find the abstract confusing: they say that a decrease in monocytes, NK cells, and lymphocytes may “serve to support ongoing immune defense.” That’s the opposite of how I’d interpret a low level of white blood cells. But maybe I’m missing something.
Sleep deprivation reduces NK and cellular immune responses in humans. The title says it all.
The study finds impairment in vigilance after sleep deprivation to 6 hours of sleep/night, increases in IL-6 secretion and, in men but not women, TNF-a, as well as decreases in cortisol.
“Relative to the partial sleep deprivation condition, subjects in the total sleep deprivation condition had elevated plasma levels of sTNF-αRI on day 2 (P = .04), day 3 (P = .01), and across days 2 to 4 of sleep loss (P = .01) and elevated levels of IL-6 on day 4 (P = .04).”
“The CRP concentrations increased during both total (88 hours awake) and partial (4.2 hours of sleep) sleep deprivation conditions, but remained stable in the control condition.”
Note that in these studies, the researchers are commonly taking frequent blood samples. For example, in that last study, they took hourly blood samples. They’re being continuously monitored, catheterized, in a lab environment, sleeping with a catheter, and getting their rectal body temperature taken. Again, I think we have to worry about the potential confounding impact of stress, blood loss, etc on driving this immune response.
Looking at the results from these 5 studies, we see a mix of effects. In sleep deprivation, sometimes inflammatory cytokines are up, but other times, inflammatory cells are down. Results are there but inconsistent.
Moreover, and crucially, these are short-term studies that don’t investigate the health impacts we’d actually care about from inflammation. That’s not their fault—they’re a valuable contrbution to scientific knowledge—but we can only learn so much from studies like this. I am not ready to accept with any great confidence a claim that “sleep deprivation shreds your immune system” based on this data.