Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.
Open accessAbstract
The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.
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In addition to infectious and chronic inflammatory conditions that involve a clear immunopathology, numerous other diseases have mild systemic elevations of inflammatory markers, including cardiovascular and metabolic diseases, certain forms of chronic pain, certain cancers, and neurodegenerative diseases.
“In addition to infectious and chronic inflammatory conditions that involve a clear immunopathology (e.g., HIV, RA), numerous other diseases emerged in the last decades for which mild systemic elevations of inflammatory markers are characteristic, including cardiovascular (481) and metabolic diseases (153), certain forms of chronic pain (23), certain cancers (165), and neurodegenerative diseases (9”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [153]
Some authors have reported no change or even a slight decrease in cortisol levels after one or several nights of total sleep deprivation.
“Indeed, some authors have reported no change [41, 43, 74, 75] or even a slight decrease in cortisol levels [76, 77] after one or several nights of total sleep deprivation.”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [75]
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- Authors
- Dinges, D. F., Douglas, S. D., Zaugg, L., Campbell, D. E., McMann, J. M., Whitehouse, W. G., Orne, E. C., Kapoor, S. C., Icaza, E., & Orne, M. T.
- Affiliations
- Pennsylvania Hospital (US)
- Children's Hospital of Philadelphia (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1994-05-01
- Volume
- 93
- Issue
- 5
- Pages
- 1930-1939
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC294300
- OpenAlex
- W2027223222
- Cited by
- 361
- References
- 43
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 14 · 2020: 13 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 13 · 2015: 19 · 2014: 18 · 2013: 15 · 2012: 13
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration
- National Institutes of Health (5p01mh044193-05)
- Ames Research Center
- National Institute of Mental Health (MH44193)
- National Center for Research Resources (CRC RR 00040)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep deprivation, leukocytosis, natural killer cells, immune function, monocytes, lymphocyte subsets, NK cell cytotoxicity, cell cycle, CD56, CD57, CD16, CD4, recovery sleep, cortisol, ACTH
- MeSH terms
- Adult, Arousal, Body Temperature, Mental Fatigue, Female, Glucocorticoids, Humans, Killer Cells, Natural, Leukocytosis, Lymphocytes, Male, Movement, Sleep Deprivation, Biomarkers
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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