title: Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance.
abstract: Cortisol and inflammatory proteins are released into the blood in response to stressors and chronic elevations of blood cortisol and inflammatory proteins may contribute to ongoing disease processes and could be useful biomarkers of disease. How chronic circadian misalignment influences cortisol and inflammatory proteins, however, is largely unknown and this was the focus of the current study. Specifically, we examined the influence of weeks of chronic circadian misalignment on cortisol, stress ratings, and pro- and anti-inflammatory proteins in humans. We also compared the effects of acute total sleep deprivation and chronic circadian misalignment on cortisol levels. Healthy, drug free females and males (N=17) aged 20-41 participated. After 3weeks of maintaining consistent sleep-wake schedules at home, six laboratory baseline days and nights, a 40-h constant routine (CR, total sleep deprivation) to examine circadian rhythms for melatonin and cortisol, participants were scheduled to a 25-day laboratory entrainment protocol that resulted in sleep and circadian disruption for eight of the participants. A second constant routine was conducted to reassess melatonin and cortisol rhythms on days 34-35. Plasma cortisol levels were also measured during sampling windows every week and trapezoidal area under the curve (AUC) was used to estimate 24-h cortisol levels. Inflammatory proteins were assessed at baseline and near the end of the entrainment protocol. Acute total sleep deprivation significantly increased cortisol levels (p<0.0001), whereas chronic circadian misalignment significantly reduced cortisol levels (p<0.05). Participants who exhibited normal circadian phase relationships with the wakefulness-sleep schedule showed little change in cortisol levels. Stress ratings increased during acute sleep deprivation (p<0.0001), whereas stress ratings remained low across weeks of study for both the misaligned and synchronized control group. Circadian misalignment significantly increased plasma tumor necrosis factor-alpha (TNF-α), interleukin 10 (IL-10) and C-reactive protein (CRP) (p<0.05). Little change was observed for the TNF-α/IL-10 ratio during circadian misalignment, whereas the TNF-α/IL-10 ratio and CRP levels decreased in the synchronized control group across weeks of circadian entrainment. The current findings demonstrate that total sleep deprivation and chronic circadian misalignment modulate cortisol levels and that chronic circadian misalignment increases plasma concentrations of pro- and anti-inflammatory proteins.
authors: Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
authors: Kenneth P
authors: KP
authors: Wright
authors: Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors: Amanda L
authors: AL
authors: Drake
authors: Sleep and Chronobiology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA; Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
authors: Danielle J
authors: DJ
authors: Frey
authors: Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA; Stress Physiology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors: Monika
authors: M
authors: Fleshner
authors: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors: Christopher A
authors: CA
authors: Desouza
authors: Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Chronobiology, Inserm U846, Stem Cell and Brain Research Institute, Bron, France; University of Lyon, Claude Bernard Lyon 1, Villeurbanne, France.
authors: Claude
authors: C
authors: Gronfier
authors: Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors: Charles A
authors: CA
authors: Czeisler
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008550:Melatonin / Q000097:blood; D012892:Sleep Deprivation / Q000097:blood*; D013312:Stress, Physiological / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein; D008550:Melatonin; D006854:Hydrocortisone
keywords: C-reactive protein; Circadian clock; Cortisol; Cytokines; Inflammation; Interleukin-10; Sleep loss; Tumor necrosis factor alpha
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