Effects of granulocyte colony-stimulating factor on night sleep in humans
Abstract
Numerous animal studies suggest that cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mediate increased sleep amount and intensity observed during infection and are, moreover, involved in physiological sleep regulation. In humans the role of cytokines in sleep-wake regulation is largely unknown. In a single-blind, placebo-controlled study, we investigated the effects of granulocyte colony-stimulating factor (G-CSF, 300 μg sc) on the plasma levels of cytokines, soluble cytokine receptors, and hormones as well as on night sleep. G-CSF did not affect rectal temperature or the plasma levels of cortisol and growth hormone but did induce increases in the plasma levels of IL-1 receptor antagonist and both soluble TNF receptors within 2 h after injection. In parallel, the amount of slow-wave sleep and electroencephalographic delta power were reduced, indicating a lowered sleep intensity. We conclude that G-CSF suppresses sleep intensity via increased circulating amounts of endogenous antagonists of IL-1β and TNF-α activity, suggesting that these cytokines are involved in human sleep regulation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sleep may facilitate energy allocation to the immune system.
“A potential explanation for this immune-supportive effect is that sleep may facilitate energy allocation to the immune system (496).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [496]
Cites
Rechtschaffen, A. (1968) · Medical Entomology and Zoology · Cited by 11,772 · see citing works
Fever: Role of Pyrogens and Cryogens
Kluger, M. J. (1991) · Physiological Reviews · doi:10.1152/physrev.1991.71.1.93 · Cited by 1,220 · see citing works
Moreira, A. L., Sampaio, E. P., Zmuidzinas, A., Frindt, P., Smith, K. A., & Kaplan, G. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.6.1675 · Cited by 1,041 · see citing works
Cytokines and the nervous system II: actions and mechanisms of action
Rothwell, N. J., & Hopkins, S. J. (1995) · Trends in Neurosciences · doi:10.1016/0166-2236(95)93890-a · Cited by 922 · see citing works
Murine tumor necrosis factor alpha is transported from blood to brain in the mouse
Gutierrez, E. G., Banks, W. A., & Kastin, A. J. (1993) · Journal of Neuroimmunology · doi:10.1016/0165-5728(93)90027-v · Cited by 577 · see citing works
Sleep-promoting effects of endogenous pyrogen (interleukin-1)
Krueger, J. M., Walter, J., Dinarello, C. A., Wolff, S. M., & CHEDID, L. A. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.246.6.r994 · Cited by 456 · see citing works
Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis
Wolkenstein, P., Latarjet, J., Roujeau, J., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(98)02197-7 · Cited by 430 · see citing works
Jacobson, J. M., Greenspan, J. S., Spritzler, J., Ketter, N., Fahey, J. L., Jackson, J. B., Fox, L., Chernoff, M., Wu, A. W., MacPhail, L. A., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199705223362103 · Cited by 411 · see citing works
Späth‐Schwalbe, E. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.5.1573 · Cited by 377 · see citing works
Recombinant tumor necrosis factor and interleukin 1 enhance slow-wave sleep
Shoham, S., Davenne, D., Cady, A. B., Dinarello, C. A., & Krueger, J. M. (1987) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1987.253.1.r142 · Cited by 290 · see citing works
Regulation of the HPA axis by cytokines.
Turnbull, A. V., & Rivier, C. (1995) · Brain, Behavior, and Immunity · doi:10.1006/brbi.1995.1026 · Cited by 289 · see citing works
Biologic and clinical effects of granulocyte colony-stimulating factor in normal individuals
Anderlini, P. N., Przepiorka, D., Champlin, R. E., et al. (1996) · Blood · doi:10.1182/blood.v88.8.2819.bloodjournal8882819 · Cited by 260 · see citing works
Effects of Clozapine on Plasma Cytokine and Soluble Cytokine Receptor Levels
Pollmächer, T., Hinze‐Selch, D., & Mullington, J. M. (1996) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199610000-00011 · Cited by 232 · see citing works
Self-citationGranowitz, E. V., Porat, R., Mier, J. W., Pribble, J. P., Stiles, D., Bloedow, D. C., Catalano, M. A., Wolff, S. M., & Dinarello, C. A. (1992) · Cytokine · doi:10.1016/1043-4666(92)90078-6 · Cited by 220 · see citing works
Exercise and Sleep: Body-Heating Effects
Horne, J., & Staff, L. H. E. (1983) · SLEEP · doi:10.1093/sleep/6.1.36 · Cited by 214 · see citing works
Steiger, A., Guldner, J., Hemmeter, U., Rothe, B., Wiedemann, K., & Holsboer, F. (2008) · Neuroendocrinology · doi:10.1159/000126275 · Cited by 209 · see citing works
Self-citationBlood-borne interleukin-1 receptor antagonist crosses the blood-brain barrier
GUTIERREZ, E., Banks, W. A., & Kastin, A. J. (1994) · Journal of Neuroimmunology · doi:10.1016/0165-5728(94)90005-1 · Cited by 176 · see citing works
Mice Lacking the TNF 55 kDa Receptor Fail to Sleep More After TNFα Treatment
Fang, J., Wang, Y., & Krueger, J. M. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05949.1997 · Cited by 167 · see citing works
Interleukin-1 derived from astrocytes enhances slow wave activity in sleep EEG of the rat
Tobler, I., Borbély, A. A., Schwyzer, M., & Fontana, A. (1984) · European Journal of Pharmacology · doi:10.1016/0014-2999(84)90391-1 · Cited by 161 · see citing works
Human responses to bacterial endotoxin.
Burrell, R. E. (1994) · PubMed · Cited by 154 · see citing works
Kapás, L., Hong, L., Cady, A. B., Opp, M. R., Postlethwaite, A. E., Seyer, J. M., & Krueger, J. M. (1992) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1992.263.3.r708 · Cited by 143 · see citing works
Influence of endotoxin on nocturnal sleep in humans
Pollmacher, T., Schreiber, W., Gudewill, S., Vedder, H., Fassbender, K., Wiedemann, K., Trachsel, L., Galanos, C., & Holsboer, F. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.6.r1077 · Cited by 119 · cited 3× · see citing works
“In humans, TNF-a is present in the circulation under baseline conditions in detectable, albeit small, amounts (16, 24, 25).”
BackgroundSelf-citationZwingenberger, K., & Wnendt, S. (1997) · PubMed · Cited by 115 · see citing works
Anti-interleukin-1 beta reduces sleep and sleep rebound after sleep deprivation in rats
Opp, M. R., & Krueger, J. M. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.266.3.r688 · Cited by 107 · see citing works
The hypothalamic-pituitary-adrenocortical system and sleep in man
Frieß, E., Wiedemann, K., Steiger, A., & Holsboer, F. (1995) · Advances in Neuroimmunology · doi:10.1016/0960-5428(95)00003-k · Cited by 104 · see citing works
Self-citationEffects of clozapine on sleep: A longitudinal study
Hinze‐Selch, D., Mullington, J. M., Orth, A., Lauer, C. J., & Pollmächer, T. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00347-2 · Cited by 99 · see citing works
Self-citationKrueger, J. M., Takahashi, S., Kapás, L., Bredow, S., Roky, R., Fang, J., Floyd, R. A., Renegar, K. B., Guha‐Thakurta, N., Novitsky, S. V., et al. (1995) · Advances in Neuroimmunology · doi:10.1016/0960-5428(95)00007-o · Cited by 98 · see citing works
Sleep, sleep deprivation and infectious disease: Studies in animals
Toth, L. A. (1995) · Advances in Neuroimmunology · doi:10.1016/0960-5428(94)00045-p · Cited by 93 · see citing works
Pollmächer, T., Korth, C., Mullington, J. M., et al. (1996) · Blood · doi:10.1182/blood.v87.3.900.bloodjournal873900 · Cited by 85 · see citing works
Self-citationGranulocyte and granulocyte-macrophage colony-stimulating factors
Steward, W. P. (1993) · The Lancet · doi:10.1016/0140-6736(93)91350-u · Cited by 85 · see citing works
Wetter, T. C., Lauer, C. J., Gillich, G., & Pollmächer, T. (1996) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(96)00022-2 · Cited by 73 · see citing works
Self-citationInhibition of tumor necrosis factor in the brain suppresses rabbit sleep
Takahashi, S., Tooley, D. D., Kap�s, L., Fang, J., Seyer, J. M., & Krueger, J. M. (1995) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00410186 · Cited by 62 · see citing works
Imeri, L., Opp, M. R., & Krueger, J. M. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.265.4.r907 · Cited by 59 · see citing works
The Effects of Fever on Sleep and Dream Patterns
Karacan, I., Wolff, S. M., Williams, R. L., Hursch, C. J., & Webb, W. B. (1968) · Psychosomatics · doi:10.1016/s0033-3182(68)71807-7 · Cited by 48 · see citing works
Influence of endotoxin on daytime sleep in humans
Korth, C., Mullington, J., Schreiber, W., & Pollmächer, T. (1996) · Infection and Immunity · doi:10.1128/iai.64.4.1110-1115.1996 · Cited by 35 · see citing works
Self-citationLancel, M., Mathias, S., Schiffelholz, T., Behl, C., & Holsboer, F. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00783-x · Cited by 16 · see citing works
Self-citationTrachsel, L. (1993) · SLEEP · doi:10.1093/sleep/16.6.586 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Sleep-Immune Crosstalk in Health and Disease
Besedovsky, L., Lange, T., & Haack, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00010.2018 · Cited by 1,479 · see citing works
Opp, M. R. (2005) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2005.01.002 · Cited by 393 · see citing works
Biochemical regulation of non-rapid-eye-movement sleep
Krueger, J. M. (2003) · Frontiers in Bioscience · doi:10.2741/1033 · Cited by 329 · see citing works
Dose-dependent effects of endotoxin on human sleep
Mullington, J., Korth, C., Hermann, D. M., Orth, A., Galanos, C., Holsboer, F., & Pollmächer, T. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.4.r947 · Cited by 226 · see citing works
Self-citationLow levels of circulating inflammatory cytokines—Do they affect human brain functions?
Pollmächer, T., Haack, M., Schuld, A., Reichenberg, A., & Yirmiya, R. (2002) · Brain, Behavior, and Immunity · doi:10.1016/s0889-1591(02)00004-1 · Cited by 202 · see citing works
Self-citationSleep enhances nocturnal plasma ghrelin levels in healthy subjects
Dzaja, A., Dalal, M. A., Himmerich, H., Uhr, M., Pollmächer, T., & Schuld, A. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00527.2003 · Cited by 184 · see citing works
Self-citationSocial regulation of leukocyte homeostasis: the role of glucocorticoid sensitivity
Cole, S. W. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.02.006 · Cited by 156 · see citing works
When grief heats up: Pro-inflammatory cytokines predict regional brain activation
O'Connor, M.-F., Irwin, M. R., & Wellisch, D. K. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.05.049 · Cited by 123 · see citing works
Brain-Immune interactions in sleep
Marshall, L., & Born, J. (2002) · International Review of Neurobiology · doi:10.1016/s0074-7742(02)52007-9 · Cited by 102 · see citing works
When grief makes you sick: Bereavement induced systemic inflammation is a question of genotype
Schultze-Florey, C. R., Martínez-Maza, O., Magpantay, L., Breen, E. C., Irwin, M. R., Gündel, H., & O’Connor, M.-F. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.06.009 · Cited by 92 · see citing works
Cole, S. W., Mendoza, S. P., & Capitanio, J. P. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181aa95a9 · Cited by 74 · see citing works
Neuroscience-driven discovery and development of sleep therapeutics
Dresler, M., Spoormaker, V. I., Beitinger, P., Czisch, M., Kimura, M., Steiger, A., & Holsboer, F. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.012 · Cited by 63 · see citing works
Self-citationSleep disruption impairs haematopoietic stem cell transplantation in mice
Rolls, A., Pang, W. W., Ibarra, I., Colas, D., Bonnavion, P., Korin, B., Heller, H. C., Weissman, I. L., & de Lecea, L. (2015) · Nature Communications · doi:10.1038/ncomms9516 · Cited by 48 · see citing works
- Authors
- Schuld, A., Mullington, J., Hermann, D., Hinze-Selch, D., Fenzel, T., Holsboer, F., & Pollmächer, T.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Max Planck Institute of Psychiatry, D-80804 Munich, Germany
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 1999-04-01
- Volume
- 276
- Issue
- 4
- Pages
- R1149-R1155
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2111759530
- Cited by
- 30
- References
- 37
- Citations by year
- 2024: 1 · 2019: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- granulocyte colony-stimulating factor, sleep regulation, cytokines, interleukin-1 receptor antagonist, soluble TNF receptors, IL-1β, TNF-α, slow-wave sleep, delta power, plasma cytokines, growth hormone, cortisol
- MeSH terms
- Adult, Body Temperature, Circadian Rhythm, Heart Rate, Humans, Hydrocortisone, Leukocyte Count, Male, Rectum, Sleep, Single-Blind Method, Granulocyte Colony-Stimulating Factor, Cytokines, Receptors, Cytokine, Human Growth Hormone
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
