Partial sleep deprivation reduces natural killer cell activity in humans.
Abstract
Sleep disturbance, measured by either subjective report or electroencephalographic (EEG) assessment of sleep, correlates with a reduction of natural killer (NK) cell activity in major depression. To test whether sleep loss independent of mood disturbance alters daytime values of cellular immune function, the effect of late-night partial sleep deprivation on NK cell activity was studied in 23 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 3 and 7 AM, NK cell activity was reduced in 18 of the 23 subjects with average lytic activity reduced significantly (p < .01) to a level 72% of the mean of three separate baseline values. After a night of resumed nocturnal sleep, NK cell activity had returned to baseline levels. These data implicate sleep in the modulation of natural immunity and demonstrate that even modest disturbances of sleep produce a reduction of NK cell activity.
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During the night of and the morning after total sleep deprivation or restriction, NK-cell activity is reduced in healthy humans.
“During both the night of and the morning after total sleep deprivation or restriction, NK-cell activity was reduced in healthy humans (253, 254, 386)”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [254]
Stimulated IL-2 production seems to be acutely enhanced by sleep in healthy humans, although other studies did not find such an effect when assessing stimulated IL-2 production specifically in CD4 T cells.
“In contrast, stimulated IL-2 production seems to be acutely enhanced by sleep in healthy humans (67, 254, 552), although other studies did not find such an effect when assessing stimulated IL-2 production specifically in CD4 T cells (62, 149).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [254]
Sleep, by favoring pro-inflammatory and Th1 cytokine production, supports the interaction between APCs and T cells and the subsequent differentiation and proliferation of Th1 cells, eventually leading to the formation of IgG1 and IgG3 antibodies.
“In addition, sleep, by favoring pro-inflammatory and Th1 cytokine production, further supports the interaction between APCs and T cells and the subsequent differentiation and proliferation of Th1 cells, eventually leading to the formation of IgG1 and IgG3 antibodies (24, 67, 148, 254, 320).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [254]
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“Lifestyle characteristics Smoking, n (column %) Never smoker Former smoker Current smoker 637 (47) 594 (44) 133 (10) 2,300 (46) 2,236 (44) 498 (10) 5,425 (46) 5,405 (46) 946 (8) 348 (42) 393 (47) 91 (11)”
InfluentialMota‐Rojas, D., Wang, D., Titto, C. G., Gómez-Prado, J., la Fuente, V. C.-D., Ghezzi, M. D., Boscato-Funes, L., Barrios-García, H., Torres-Bernal, F., Casas-Alvarado, A., et al. (2021) · Animals · doi:10.3390/ani11082316 · Cited by 69 · see citing works
Inflammation at the Intersection of Behavior and Somatic Symptoms
Irwin, M. R. (2011) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2011.05.005 · Cited by 69 · see citing works
“nitial studies demonstrated that sleep loss results in decreases in innate immunity as eflected by decreases in the activity of natural killer cells.(59,60) However, sleep loss can also have activating effects on certain aspects of the immune system, leading to increases in increases in inflammatory markers such as IL…”
Self-citationIrwin, M. R. (2022) · Temperature · doi:10.1080/23328940.2022.2109932 · Cited by 76 · see citing works
“Indeed, partial night sleep deprivation, either early- or late night, leads to robust reductions in morning levels NK activity [80,124], as well as sensitivity of NK cells to IL-2 activation [80], findings which parallel the suppressive effects of sleep deprivation on adaptive immune responses.”
BackgroundSelf-citationImpact of partial sleep deprivation on immune markers
Wilder‐Smith, A., Mustafa, F., Earnest, A., Gen, L., & MacAry, P. A. (2013) · Sleep Medicine · doi:10.1016/j.sleep.2013.07.001 · Cited by 65 · see citing works
“, reduced natural killer cell activity, suppressed IL-2 production) [2,4,5], as well as increased circulating levels of inflammatory markers (i.”
BackgroundSavard, J., Miller, S. M., Mills, M., O'Leary, A., Harding, H., Douglas, S. D., Mangan, C. E., Belch, R., & Winokur, A. (1999) · Psychosomatic Medicine · doi:10.1097/00006842-199907000-00014 · Cited by 62 · see citing works
“This paradigm has been found to lead to immunosuppressive effects, including a reduction in NK cells, NK cell activity, lymphokine activated killer cell activity, and the production of interleukin-2 ( 42 , 43).”
BackgroundResultInfluentialda Silva, F. R., Guerreiro, R. D. C., Andrade, H. D. A., Stieler, E., Silva, A., & de Mello, M. T. (2020) · Chronobiology International · doi:10.1080/07420528.2020.1756841 · Cited by 63 · see citing works
Zager, A., Andersen, M. L., Lima, M. M. S., Reksidler, A. B., Machado, R. B., & Tufik, S. (2009) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2009.03.005 · Cited by 63 · see citing works
“, 2003), overall host defense (Irwin et al., 1994; Irwin et al., 1996) and general health (Wingard and Berkman, 1983; Kripke et al.”
BackgroundCHRONIC FATIGUE SYNDROME AND FIBROMYALGIA
Demitrack, M. A. (1998) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70031-9 · Cited by 63 · see citing works
Reduction of Natural Killer Cytotoxic Activity in Major Depression
Jung, W., & Irwin, M. R. (1999) · Psychosomatic Medicine · doi:10.1097/00006842-199905000-00002 · Cited by 61 · see citing works
“These data, together with observations that sleep disturbance is correlated with a reduction of NK activity (34, 51 , 52), suggest a role of disordered sleep in mediating the relationship between depression, smoking, and a reduction of lytic activity.”
BackgroundSelf-citationPhillips, K. D., Sowell, R. L., Boyd, M. R., Dudgeon, W. D., & Hand, G. A. (2005) · Quality of Life Research · doi:10.1007/s11136-004-2574-0 · Cited by 58 · see citing works
Ironson, G. H., Balbin, E., Solomon, G. F., Fahey, J. L., Klimas, N. G., Schneiderman, N., & FLETCHER, M. A. (2001) · AIDS · doi:10.1097/00002030-200111090-00001 · Cited by 60 · see citing works
“variables (such as stressful life events [13±19], alcohol and drug use [20], sleep [16,21], socioeconomic status [22] and sexually transmitted diseases (STD) [23]) as well as neuroendocrine mechanisms involved in stress (such as cortisol [24,25]), secondary analyses were performed to rule out such factors (confounding…”
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Locus of control, neuroticism, and stressors: Combined influences on reported physical illness
Horner, K. L. (1996) · Personality and Individual Differences · doi:10.1016/0191-8869(96)00067-0 · Cited by 58 · see citing works
Landis, C. A., Lentz, M. J., Tsuji, J. M., Buchwald, D., & Shaver, J. L. F. (2003) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2003.11.001 · Cited by 59 · see citing works
Circulating Lymphocyte Subsets in Major Depression and Dysthymia With Typical or Atypical Features
Ravindran, A. V., Griffiths, J., Merali, Z., & Anisman, H. (1998) · Psychosomatic Medicine · doi:10.1097/00006842-199805000-00013 · Cited by 59 · see citing works
“Although functional immune measures were not determined in the present study, when considered in conjunction with reports that alterations of sleep may affect NK cytotoxicty and cytokine activity (14, 15), it seems clear that analysis of the depression-immune profile should consider the specific symptoms and chronicit…”
BackgroundActigraphy for Measurement of Sleep and Sleep-Wake Rhythms in Relation to Surgery
Madsen, M. T., Rosenberg, J., & Gögenür, I. (2013) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.2598 · Cited by 57 · see citing works
Sleep Disturbance After Burn Injury
Boeve, S. A., Aaron, L. A., Martin-Herz, S. P., Peterson, A., Cain, V., Heimbach, D. M., & Patterson, D. R. (2002) · Journal of Burn Care & Rehabilitation · doi:10.1097/00004630-200201000-00007 · Cited by 57 · see citing works
Sleep, cytokines and immune function
Dickstein, J. B. (1999) · Sleep Medicine Reviews · doi:10.1016/s1087-0792(99)90003-5 · Cited by 56 · see citing works
Spilsbury, J. C. (2009) · Behavioral Sleep Medicine · doi:10.1080/15402000903190207 · Cited by 53 · see citing works
“The investigators noted that their findings corresponded with previous research showing that sleep deprivation in normal, unstressed persons reduced natural killer cell cytotoxicity (Irwin et al., 1994).”
ResultAbe, M., & Abe, H. (2019) · Personalized Medicine Universe · doi:10.1016/j.pmu.2019.05.002 · Cited by 52 · see citing works
Sleep Quality and Sleep Hygiene Behaviors of Adolescents during Chemotherapy
Walker, A. J., Johnson, K., Miaskowski, C. A., Lee, K. A., & Gedaly‐Duff, V. (2010) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.27932 · Cited by 51 · see citing works
- Authors
- Irwin, M., Mascovich, A., Gillin, J. C., Willoughby, R., Pike, J., & Smith, T. L.
- Affiliations
- University of California San Diego (US)
- ORCID
- Irwin, M
- Venue
- Psychosomatic Medicine
- Published
- 1994-11
- Volume
- 56
- Issue
- 6
- Pages
- 493-498
- ISSN
- 0033-3174 (ISSN-L)
- OpenAlex
- W2047973327
- Cited by
- 249
- References
- 0
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 12 · 2021: 12 · 2020: 5 · 2019: 8 · 2018: 2 · 2017: 6 · 2016: 8 · 2015: 12 · 2014: 3 · 2013: 10 · 2012: 9
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychosomatic Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01mh046867-01a2)
- National Institute of Mental Health (MH-46867-01, MH30914)
- National Center for Research Resources (M-01RR00827, M01RR000827)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep restriction, natural killer cells, cellular immune function, sleep disorders, natural immunity, major depressive disorder, nocturnal sleep, lytic activity
- MeSH terms
- Adult, Electroencephalography, Humans, Immunity, Cellular, Killer Cells, Natural, Lymphocytes, Male, Middle Aged, Sleep Deprivation, Sleep Stages, Sleep, REM, Stress, Psychological, Polysomnography
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