You're lying awake in bed at 4 am. - it's another sleepless night. Your legs are twitching and pulsating, your mind is racing aimlessly with blurred abstract nonsense and the giant purple bags under your eyes continue to darken and grow larger.
Yes, we've all been there.
The last thing you need to hear is that your STRESS and LACK OF SLEEP are actually making the problem WORSE!
But, it's the truth.
And now that you know this, you can do something about it.
As the powerful influence of inflammation continues to move to the forefront of the media, more and more studies are being done to find out just how widespread its effects are. This includes studies I'll present to you on this website showing that both stress and insomnia increase inflammation levels.
This page provides scientific evidence that insomnia increases inflammation levels.
For information on how stress increases inflammation levels, please visit the page
Studies Showing How Stress Increases Inflammation Levels .
"Sleep Loss and Inflammation."
Janet M. Mullington, Ph.D., Norah S. Simpson, Ph.D., Hans K. Meier-Ewert, M.D. and Monika Haack, Ph.D.. Best Pract Res Clin Endocrinol Metab. Oct 2010; 24(5): 775784.
doi: 10.1016/j.beem.2010.08.014
ABSTRACT:
Controlled, experimental studies on the effects of acute sleep loss in humans have shown that mediators of inflammation are altered by sleep loss. Elevations in these mediators have been found to occur in healthy, rigorously screened individuals undergoing experimental vigils of more than 24 hours, and have also been seen in response to various durations of sleep restricted to between 25 and 50% of a normal 8 hour sleep amount. While these altered profiles represent small changes, such sub-clinical shifts in basal inflammatory cytokines are known to be associated with the future development of metabolic syndrome disease in healthy, asymptomatic individuals. Although the mechanism of this altered inflammatory status in humans undergoing experimental sleep loss is unknown, it is likely that autonomic activation and metabolic changes play key roles.
DISCUSSION:
While the discussions in this paper have focused on experimental sleep loss in healthy populations and possible mechanisms of inflammation, elevations of inflammatory markers have also been reported in clinical populations of disturbed sleep, including insomnia and sleep apnea. Furthermore, patients experiencing chronic pain frequently have elevated inflammatory mediators and impaired sleep. Inflammatory markers, including prostaglandins and pro-inflammatory cytokines, have been shown to sensitize nociceptors (i.e., decreasing their response threshold), thereby contributing to the development and/or amplification of spontaneous pain and hyperalgesia. Indeed, experimental sleep loss in healthy adults leads to generalized pain by self-report and the experience is correlated with increased prostaglandin E2 and IL-6, suggesting a mediating role of inflammatory markers in the connection of sleep loss and pain that needs to be explored in future research.
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"Sleep Restriction Increases the Risk of Developing Cardiovascular Diseases by Augmenting Proinflammatory Responses through IL-17 and CRP."
Wessel M. A. van Leeuwen, Maili Lehto, Piia Karisola, Harri Lindholm, Ritva Luukkonen, Mikael Sallinen, Mikko Hrm, Tarja Porkka-Heiskanen and Harri Alenius. PLoS One. 2009;4(2):e4589. doi: 10.1371/journal.pone.0004589. Epub 2009 Feb 25.
BACKGROUND:
Sleep restriction, leading to deprivation of sleep, is common in modern 24-h societies and is associated with the development of health problems including cardiovascular diseases. Our objective was to investigate the immunological effects of prolonged sleep restriction and subsequent recovery sleep, by simulating a working week and following recovery weekend in a laboratory environment.
METHODS AND FINDINGS:
After 2 baseline nights of 8 hours time in bed (TIB), 13 healthy young men had only 4 hours TIB per night for 5 nights, followed by 2 recovery nights with 8 hours TIB. 6 control subjects had 8 hours TIB per night throughout the experiment. Heart rate, blood pressure, salivary cortisol and serum C-reactive protein (CRP) were measured after the baseline (BL), sleep restriction (SR) and recovery (REC) period. Peripheral blood mononuclear cells (PBMC) were collected at these time points, counted and stimulated with PHA. Cell proliferation was analyzed by thymidine incorporation and cytokine production by ELISA and RT-PCR. CRP was increased after SR (145% of BL; p<0.05), and continued to increase after REC (231% of BL; p<0.05). Heart rate was increased after REC (108% of BL; p<0.05). The amount of circulating NK-cells decreased (65% of BL; p<0.005) and the amount of B-cells increased (121% of BL; p<0.005) after SR, but these cell numbers recovered almost completely during REC. Proliferation of stimulated PBMC increased after SR (233% of BL; p<0.05), accompanied by increased production of IL-1beta (137% of BL; p<0.05), IL-6 (163% of BL; p<0.05) and IL-17 (138% of BL; p<0.05) at mRNA level. After REC, IL-17 was still increased at the protein level (119% of BL; p<0.05).
CONCLUSIONS:
5 nights of sleep restriction increased lymphocyte activation and the production of proinflammatory cytokines including IL-1beta IL-6 and IL-17; they remained elevated after 2 nights of recovery sleep, accompanied by increased heart rate and serum CRP, 2 important risk factors for cardiovascular diseases. Therefore, long-term sleep restriction may lead to persistent changes in the immune system and the increased production of IL-17 together with CRP may increase the risk of developing cardiovascular diseases.
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"Sleep duration and biomarkers of inflammation."
Patel SR, Zhu X, Storfer-Isser A, Mehra R, Jenny NS, Tracy R, Redline S. Sleep. 2009 Feb;32(2):200-4.
INTRODUCTION:
Extremes of sleep duration have been associated with adverse health outcomes. The mechanism is unclear but may be related to increased inflammation. We sought to assess the association between sleep duration and inflammatory biomarkers.
METHODS:
A total of 614 individuals from the Cleveland Family Study completed questionnaires about sleep habits and underwent polysomnography. A morning fasting blood sample was assayed for 5 inflammatory cytokines.
RESULTS:
In this cohort, mean (SD) habitual sleep duration based on self-report was 7.6 (1.6) h and mean sleep duration by polysomnography (PSG) on the night prior to blood sampling was 6.2 (1.3) h. After adjusting for obesity and apnea severity, each additional hour of habitual sleep duration was associated with an 8% increase in C-reactive protein (CRP) levels (P=0.004) and 7% increase in interleukin-6 (IL-6) levels (P=0.0003). These associations were independent of self-reported sleepiness. In contrast, PSG sleep duration was inversely associated with tumor necrosis factor alpha (TNFa) levels. For each hour reduction in sleep, TNFalpha levels increased by 8% on average (P=0.02). Sleep duration was not associated with IL-1 or IL-10.
CONCLUSIONS:
Increases in habitual sleep durations are associated with elevations in CRP and IL-6 while reduced PSG sleep duration is associated with elevated TNFa levels. Activation of pro-inflammatory pathways may represent a mechanism by which extreme sleep habits affect health.
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Sleep Loss Activates Cellular Inflammatory Signaling
Michael R. Irwin, Minge Wang, Denise Ribeiro, Hyong Jin Cho, Richard Olmstead, Elizabeth Crabb Breen, Otoniel Martinez-Maza and Steve Cole. Biol Psychiatry. 2008 Sep 15;64(6):538-40. doi: 10.1016/j.biopsych.2008.05.004. Epub 2008 Jun 17.
BACKGROUND:
Accumulating evidence suggests that sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. This study was undertaken to test the effects of sleep loss on activation of nuclear factor (NF)-kappaB, a transcription factor that serves a critical role in the inflammatory signaling cascade.
METHODS:
In 14 healthy adults (seven women; seven men), peripheral blood mononuclear cell NF-kappaB was repeatedly assessed, along with enumeration of lymphocyte subpopulations, in the morning after baseline sleep, partial sleep deprivation (awake from 11 pm to 3:00 am), and recovery sleep.
RESULTS:
In the morning after a night of sleep loss, mononuclear cell NF-kappaB activation was significantly greater compared with morning levels following uninterrupted baseline or recovery sleep, in which the response was found in female but not in male subjects.
CONCLUSIONS:
These results identify NF-kappaB activation as a molecular pathway by which sleep disturbance may influence leukocyte inflammatory gene expression and the risk of inflammation-related disease.
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"Chronic Insomnia and Stress System."
Maria Basta, M.D., George P Chrousos, M.D, Antonio Vela-Bueno, M.D and Alexandros N Vgontzas, M.D. Sleep Med Clin. Jun 2007; 2(2): 279 291. doi: 10.1016/j.jsmc.2007.04.002
SYNOPSIS:
In insomnia, which is a very common sleep disorder, objective sleep measures, EEG activity, physiologic findings, HPA axis activity and inflammation markers suggest that it is not a state of sleep loss, but a disorder of hyperarousal present both during the night and the daytime. Several psychological and physiological factors contribute to the onset and perpetuation of insomnia, such as anxious-ruminative personality traits, stressful events, age-related sleep homeostasis weakening mechanisms, menopause and biologic genetic diathesis of CNS hyperarousal. The therapeutic approach in insomnia should be multidimensional reducing the overall emotional and physiologic hyperarousal and its underlying factors present throughout the 24-h sleep/wake period.
Data from studies on objective sleep, EEG activity, physiologic findings, neuroimaging, neuro-cognitive function and HPA axis and inflammation markers suggest that insomnia is not a state of sleep loss, but a disorder of hyperarousal present both during the night and the daytime.
The finding that pro-inflammatory cytokines' IL-6 and TNFa daytime secretion is elevated in insomniacs, considering their role in subjective complaints of fatigue and poor performance, may lead to novel approaches to treat insomnia. There are unpublished reports that insomniacs use anti-inflammatory medications to fight fatigue and even improve their sleep. These reports are more frequent among elderly insomniacs. Particularly, in the elderly insomniacs, even if they do not have an active inflammatory disease, strategies to reduce low-grade inflammation by administration of sex steroids, decreasing fat through diet and exercise, and controlling adequately chronic pain and inflammation with non-steroid anti-inflammatory agents, may improve sleep, daytime alertness, and performance, which in tern, may decrease the risk of common diseases of old age, such as metabolic and cardiovascular problems, cognitive disorders, and osteoporosis.
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"The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults."
Frey DJ, Fleshner M, Wright KP Jr. Brain Behav Immun. 2007 Nov;21(8):1050-7. Epub 2007 May 23.
ABSTRACT:
Inflammatory cytokines are released in response to stress, tissue damage, and infection. Acutely, this response is adaptive; however, chronic elevation of inflammatory proteins can contribute to health problems including cardiovascular, endocrine, mood, and sleep disorders.
Nineteen healthy men and women aged 28.05+/-8.56 (mean+/-SD) were totally sleep deprived for 40 h under constant routine conditions.
Pro-inflammatory markers: intracellular adhesion molecule-1 (ICAM-1), E-selectin, vascular adhesion molecule-1 (VCAM-1), c-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta), and the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) were assayed in plasma. Daytime levels during baseline (hours 1-15 of scheduled wakefulness) were compared to daytime levels during sleep deprivation (hours 25-39 of scheduled wakefulness), thus controlling for circadian phase within an individual. Repeated measures ANOVA with planned comparisons showed that 40 h of total sleep deprivation induced a significant increase in E-selectin, ICAM-1, IL-1beta, and IL-1ra, a significant decrease in CRP and IL-6, and no significant change in VCAM-1. Alterations in circulating levels of pro- and anti-inflammatory cytokines and cell adhesion molecules during sleep deprivation were consistent with both increased and decreased inflammation.
These findings suggest that one night of sleep loss triggers a stress response that includes stimulation of both pro- and anti-inflammatory proteins in the healthy young subjects tested under our experimental conditions.
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"Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation."
Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A and Cole S. Arch Intern Med. 2006 Sep 18;166(16):1756-62.
BACKGROUND:
Inflammation is associated with increased risk of cardiovascular disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known.
METHODS:
In 30 healthy adults, monocyte intracellular proinflammatory cytokine production was repeatedly assessed during the day across 3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3 am). We analyzed the impact of sleep loss on transcription of proinflammatory cytokine genes and used DNA microarray analyses to characterize candidate transcription-control pathways that might mediate the effects of sleep loss on leukocyte gene expression.
CONCLUSIONS:
Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.
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"Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk."
Meier-Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, Mullington JM. J Am Coll Cardiol. 2004 Feb 18;43(4):678-83.
OBJECTIVES:
We sought to investigate the effects of sleep loss on high-sensitivity C-reactive protein (CRP) levels.
BACKGROUND:
Concentrations of high-sensitivity CRP are predictive of future cardiovascular morbidity. In epidemiologic studies, short sleep duration and sleep complaints have also been associated with increased cardiovascular morbidity. Two studies were undertaken to examine the effect of acute total and short-term partial sleep deprivation on concentrations of high-sensitivity CRP in healthy human subjects.
METHODS:
In Experiment 1, 10 healthy adult subjects stayed awake for 88 continuous hours. Samples of high-sensitivity CRP were collected every 90 min for 5 consecutive days, encompassing the vigil. In Experiment 2, 10 subjects were randomly assigned to either 8.2 h (control) or 4.2 h (partial sleep deprivation) of nighttime sleep for 10 consecutive days. Hourly samples of high-sensitivity CRP were taken during a baseline night and on day 10 of the study protocol.
RESULTS:
The CRP concentrations increased during both total and partial sleep deprivation conditions, but remained stable in the control condition. Systolic blood pressure increased across deprivation in Experiment 1, and heart rate increased in Experiment 2.
CONCLUSIONS:
Both acute total and short-term partial sleep deprivation resulted in elevated high-sensitivity CRP concentrations, a stable marker of inflammation that has been shown to be predictive of cardiovascular morbidity. We propose that sleep loss may be one of the ways that inflammatory processes are activated and contribute to the association of sleep complaints, short sleep duration, and cardiovascular morbidity observed in epidemiologic surveys.
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