The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index.
Sleep enhances IL‐6 trans‐signaling in humans
Abstract
Sleep is commonly considered to support immune defense. The underlying sleep‐immune interaction appears to rely critically on cytokines, like interleukin‐6 (IL‐6), that combine effects on immune and neuronal functions. The IL‐6 signal is conveyed in two ways: it stimulates a restricted group of (mostly immune) cells via membrane‐bound IL‐6 receptors (mIL‐6R) by forming a complex with soluble IL‐6R (sIL‐6R), and it stimulates (via membrane‐bound gp130) a great variety of other cell types—a process termed trans ‐signaling. Focusing on the receptor side of IL‐6 signaling, we examined the effect of sleep on sIL‐6R plasma concentrations, mIL‐6R expression, plasma sgp130, and numbers of IL‐6‐producing monocytes in healthy humans who were tested during a regular sleep‐wake cycle and 24 h of wakefulness while blood was sampled repeatedly. Sleep strongly enhanced concentrations of sIL‐6R, exceeding wake levels by 70% at the end of sleep. This rise was due to an increase in the PC (proteolytic cleavage) rather than the DS (differentially spliced) variant of sIL‐6R. Sleep did not affect IL‐6‐producing monocytes, mIL‐6R density, or sgp130 concentrations. The selective increase in sIL‐6R implicates an enhanced trans ‐signaling capacity whereby sleep distinctly widens the profile of IL‐6 actions, enabling an integrated influence on brain and peripheral organs.—Dimitrov, S., Lange, T., Benedict, C., Nowell, M. A., Jones, S. A., Scheller, J., Rose‐John, S., Born, J. Sleep enhances IL‐6 trans‐signaling in humans. FASEB J. 20, E1599 –E1609 (2006)
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“Dimitrov et al (2006) have found that monocyte production of IL-6 also peaks at 0200 hours even in the midst of sleep deprivation.”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Dimitrov et al, 2006
In the citing paper
“Along with nocturnal increase in IL-6, there is a robust increase in circulating levels of IL-6R (Dimitrov and Lange et al, 2006).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Dimitrov and Lange et al, 2006
In the citing paper
“Similarly, total monocyte counts, lymphocyte counts, and the major lymphocyte subsets (i.e., B cells, CD4 and CD8 T cells, NK cells), have been found to be either reduced by sleep (46, 67, 148, 251, 254, 480, 556, 580) or unchanged (3, 69, 103, 122, 152, 178, 224, 234, 263, 338, 418, 463, 469) when compared with acute or prolonged sleep reduction in humans.”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [148]
In the citing paper
“sleep might rather support the migration of lymphocytes, thus supporting the formation of immunological memory.”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [148]
In the citing paper
“Sleep reduces the number of APCs and T cells in the blood, probably by redistributing these cells to lymph nodes (67, 143, 148, 169)”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [148]
In the citing paper
“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 [148]
Citations
Cites
Rechtschaffen, A. (1968) · Medical Entomology and Zoology · Cited by 11,772
Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-α,in Vivo1
Mohamed‐Ali, V., Goodrick, S., Rawesh, A., Katz, D. R., Miles, J. M., Yudkin, J. S., Klein, S., & Coppack, S. W. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4450 · Cited by 2,032
Fried, S. K., Bunkin, D. A., & Greenberg, A. S. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.3.4660 · Cited by 1,756
Adverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines
Vgontzas, A. N., Zoumakis, E., Bixler, E. O., Lin, H.-M., Follett, H., Kales, A., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031562 · Cited by 1,050
Hurst, S. M., Wilkinson, T. S., McLoughlin, R. M., Jones, S., Horiuchi, S., Yamamoto, N., Rose-John, S., Fuller, G. M., Topley, N., & Jones, S. A. (2001) · Immunity · doi:10.1016/s1074-7613(01)00151-0 · Cited by 811
Self-citationSoluble receptors for cytokines and growth factors: generation and biological function
Rose‐John, S., & Heinrich, P. C. (1994) · Biochemical Journal · doi:10.1042/bj3000281 · Cited by 777
Self-citationSubcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor- , in Vivo
Mohamed-Ali, V. (1997) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.12.4196 · Cited by 717
The soluble interleukin 6 receptor: mechanisms of production and implications in disease
Jones, S. A., Horiuchi, S., Topley, N., Yamamoto, N., & Fuller, G. M. (2001) · The FASEB Journal · doi:10.1096/fj.99-1003rev · Cited by 628
Self-citationSick and tired: does sleep have a vital role in the immune system?
Bryant, P. A., Trinder, J., & Curtis, N. (2004) · Nature Reviews Immunology · doi:10.1038/nri1369 · Cited by 551
Circadian Interleukin-6 Secretion and Quantity and Depth of Sleep
Vgontzas, A. N., Papanicolaou, D. A., Bixler, E. O., Lotsikas, A., Zachman, K., Kales, A., Prolo, P., Wong, M.-L., Licinio, J., Gold, P. W., et al. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.8.5894 · Cited by 516
Shearer, W. T., Reuben, J. M., Mullington, J. M., Price, N. J., Lee, B.-N., Smith, E. O., Szuba, M. P., Van Dongen, H. P. A., & Dinges, D. F. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.112270 · Cited by 455
Späth‐Schwalbe, E. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.5.1573 · Cited by 377
Redwine, L. S., Hauger, R. L., Gillin, J. C., & Irwin, M. R. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6871 · Cited by 373
Effects of sleep and sleep loss on immunity and cytokines
Irwin, M. R. (2002) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00003-x · Cited by 368
Doganci, A., Eigenbrod, T., Krug, N., Sanctis, G. T. D., Hausding, M., Erpenbeck, V. J., Haddad, E., Schmitt, E., Bopp, T., Kallen, K.-J., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22433 · Cited by 364
Self-citationCytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.
Brattsand, R., & Linden, M. (1996) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1996.22164025.x · Cited by 361
Sympathetic neurons can produce and respond to interleukin 6.
März, P., Cheng, J. G., Gadient, R., Patterson, P. H., Stoyan, T., Otten, U., & Rose-John, S. (1998) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.95.6.3251 · Cited by 346
Self-citationVgontzas, A. N., Zoumakis, E., Lin, H. ‐., Bixler, E. O., Trakada, G., & Chrousos, G. P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031929 · Cited by 345
IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation
McLoughlin, R. M., Jenkins, B. J., Grail, D., Williams, A. S., Fielding, C. A., Parker, C. R., Ernst, M., Topley, N., & Jones, S. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501794102 · Cited by 340
Self-citationIL-6 and its circadian secretion in humans
Vgontzas, A. N., Bixler, E. O., Lin, H.-M., Prolo, P., Trakada, G., & Chrousos, G. P. (2005) · Neuroimmunomodulation · doi:10.1159/000084844 · Cited by 338
Interleukin‐6: a cytokine to forget
Balschun, D., Wetzel, W., del Rey, A., Pitossi, F. J., Schneider, H., Zuschratter, W., & Besedovsky, H. O. (2004) · The FASEB Journal · doi:10.1096/fj.04-1625fje · Cited by 317
Doganci, A., Eigenbrod, T., Krug, N., Sanctis, G. T. D., Hausding, M., Erpenbeck, V. J., Haddad, E., Schmitt, E., Bopp, T., Kallen, K.-J., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522433 · Cited by 304
Self-citationRedwine, L. S. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.10.3597 · Cited by 285
The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome
Çiftçi, T. U., Köktürk, O., Bukan, N. C., & Bi̇lgi̇han, A. (2004) · Cytokine · doi:10.1016/j.cyto.2004.07.003 · Cited by 280
Links between the innate immune system and sleep
Majde, J. A., & Krueger, J. M. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.08.005 · Cited by 277
Nowell, M. A., Richards, P. J., Horiuchi, S., Yamamoto, N., Rose‐John, S., Topley, N., Williams, A. S., & Jones, S. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.6.3202 · Cited by 269
Self-citationMojón, A., Fernández, J. R., & Hermida, R. C. (1992) · Chronobiology International · doi:10.3109/07420529209064552 · Cited by 268
Review: IL-6 Transsignaling: The In Vivo Consequences
Jones, S. A., Richards, P. J., Scheller, J., & Rose‐John, S. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.241 · Cited by 254
Self-citationTancredi, V., D’Antuono, M., Café, C., Giovedı̀, S., Buè, M. C., D’Arcangelo, G., Onofri, F., & Benfenati, F. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750634.x · Cited by 249
Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans
Dimitrov, S., Lange, T., Tieken, S., Fehm, H. L., & Born, J. (2004) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2003.08.004 · Cited by 209
Self-citationC-reactive Protein: A Physiological Activator of Interleukin 6 Receptor Shedding
Jones, S. A., Novick, D., Horiuchi, S., Yamamoto, N., Szalai, A. J., & Fuller, G. M. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.3.599 · Cited by 200
Self-citationPlasma cytokine levels in patients with obstructive sleep apnea syndrome: a preliminary study
Alberti, A., Sarchielli, P., Gallinella, E., Floridi, A., Floridi, A., Mazzotta, G., & Gallai, V. (2003) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2003.00361.x · Cited by 191
McLoughlin, R., Hurst, S., Nowell, M., Harris, D., Horiuchi, S., Morgan, L. W., Wilkinson, T. S., Yamamoto, N., Topley, N., & Jones, S. A. (2004) · Journal of Immunology · doi:10.4049/jimmunol.172.9.5676 · Cited by 170
Self-citationPetrovsky, N., & Harrison, L. C. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.11.5163 · Cited by 168
Obál, F., & Krueger, J. M. (2004) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2004.03.005 · Cited by 166
Humoral Links between Sleep and the Immune System
Krueger, J. M., & Majde, J. A. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03133.x · Cited by 163
Towards a unified model of neuroendocrine–immune interaction
Petrovsky, N. (2001) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.2001.01029.x · Cited by 160
Soluble interleukin-6 (IL-6) receptor augments central effects of IL-6 in vivo.
Schöbitz, B., Pezeshki, G., Pohl, T., Hemmann, U., Heinrich, P. C., Holsboer, F., & Reul, J. M. H. M. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.8.7768358 · Cited by 159
Davis, K. A., Abrams, B., Iyer, S. B., Hoffman, R. A., & Bishop, J. E. (1998) · Cytometry · doi:10.1002/(sici)1097-0320(19981001)33:2 · Cited by 151
Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man.
Späth-Schwalbe, E., Born, J., Schrezenmeier, H., Bornstein, S. R., Stromeyer, P., Drechsler, S., Fehm, H. L., & Porzsolt, F. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.4.7962296 · Cited by 145
Cutolo, M., SERIOLO, B., Craviotto, C., Pizzorni, C., & Sulli, A. (2003) · Annals of the Rheumatic Diseases · doi:10.1136/ard.62.7.593 · Cited by 136
Sutherland, E. R. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.09.028 · Cited by 115
Diurnal variations of interleukin-6 plasma levels are confounded by blood drawing procedures
Haack, M., Kraus, T., Schuld, A., Dalal, M. A., Koethe, D., & Pollmächer, T. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00006-9 · Cited by 113
Humoral regulation of physiological sleep: cytokines and GHRH
Krueger, Obál, Jr., & Fang (1999) · Journal of Sleep Research · doi:10.1046/j.1365-2869.1999.00009.x · Cited by 112
Chen, Q., Wang, W., Bruce, R., Li, H., Schleider, D. M., Mulbury, M. J., Bain, M. D., Wallace, P. K., Baumann, H., & Evans, S. S. (2004) · Immunity · doi:10.1016/s1074-7613(03)00358-3 · Cited by 110
Circadian characteristics of circulating interleukin-6 in men
Sothern, R. B., Roitman-Johnson, B., Kanabrocki, E. L., Yager, J. G., Roodell, M. M., Weatherbee, J. A., Young, M. R. I., Nemchausky, B. M., & Scheving, L. E. (1995) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(95)70104-4 · Cited by 106
Interrelationships between growthhormone and sleep
Cauter, E. V., & Copinschi, G. (2000) · Growth Hormone & IGF Research · doi:10.1016/s1096-6374(00)80011-8 · Cited by 104
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
Hu, J., Chen, Z., Gorczynski, C. P., Gorczynski, L. Y., Kai, Y., Lee, L., Manuel, J., & Gorczynski, R. M. (2003) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2003.03.001 · Cited by 101
Rose‐John, S., & Neurath, M. F. (2004) · Immunity · doi:10.1016/s1074-7613(04)00003-2 · Cited by 98
Self-citationDynamics of the gp130 cytokine complex: A model for assembly on the cellular membrane
Schroers, A., Hecht, O., Kallen, K., Pachta, M., Rose‐John, S., & Grötzinger, J. (2005) · Protein Science · doi:10.1110/ps.041117105 · Cited by 78
Self-citationInterleukin-6 biology is coordinated by membrane bound and soluble receptors.
Rose‐John, S. (2003) · Acta Biochimica Polonica · doi:10.18388/abp.2003_3654 · Cited by 77
Self-citationA manual of standardized terminology, techniques and scoring system for sleep of human subjects
Rechtschaffen, A. (1968) · Medical Entomology and Zoology · Cited by 60
Interleukin-6 receptor signaling. II. Bio-availability of interleukin-6 in serum.
Gaillard, J., Pugnière, M., Tresca, J., Mani, J. C., Klein, B., & Brochier, J. (1999) · PubMed · Cited by 50
Adamopoulos, S. N., Parissis, J., Georgiadis, M., Karatzas, D., Paraskevaidis, J., Κroupis, C., Karavolias, G., Koniavitou, K., & Kremastinos, D. T. (2002) · American Heart Journal · doi:10.1067/mhj.2002.124052 · Cited by 50
Interleukin-6 levels fluctuate with the light–dark cycle in the brain and peripheral tissues in rats
Guan, Z., Vgontzas, A. N., Omori, T., Peng, X., Bixler, E. O., & Fang, J. (2005) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.01.005 · Cited by 50
Franchimont, N., Lambert, C., Huynen, P., Ribbens, C., Relić, B., Chariot, A., Bours, V., Piette, J. G., Merville, M., & Malaise, M. (2005) · Arthritis & Rheumatism · doi:10.1002/art.20727 · Cited by 46
HORIUCHI, AMPOFO, Koyanagi, Yamashita, Waki, MATSUMOTO, YAMAMOTO, & YAMAMOTO (1998) · Immunology · doi:10.1046/j.1365-2567.1998.00622.x · Cited by 33
Cichy, J., Rose‐John, S., Potempa, J., Pryjma, J. R., & Travis, J. W. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.11.5648 · Cited by 21
Self-citationŠereš, J., Herichová, I., Roman, O., Bornstein, S. R., & Jur̀čovičová, J. (2004) · NeuroImmunoModulation · doi:10.1159/000079412 · Cited by 16
Flagged first, then by citations
1 of the 61 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- 10.1210/jc.79.4.1212 · DOI · Paper page
- Janke W., 1978, Die Eigenschaftswörterliste (EWL)
- 10.1210/jc.83.3.847 · DOI
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
“Sleep can show enhancing (180, 200, 464), decreasing (541, 562, 563) or no effects (67, 104, 147, 224, 261, 489) on IL-6 levels in plasma or saliva when compared with one night with no or restricted sleep in healthy participants.”
BackgroundSelf-citationWhy Sleep Is Important for Health: A Psychoneuroimmunology Perspective
Irwin, M. R. (2015) · Annual Review of Psychology · doi:10.1146/annurev-psych-010213-115205 · Cited by 1,325
“%) increase in levels of soluble IL-6R (Dimitrov et al. 2006), which is most pronounced during the late part of the night, consistent with relative increases in REM sleep amounts and increases in IL-6 (Redwine et al. 2000).”
BackgroundBesedovsky, L., Lange, T., & Born, J. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-1044-0 · Cited by 1,153
Self-citationSleep and inflammation: partners in sickness and in health
Irwin, M. R. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0190-z · Cited by 1,138
Rose-John, S. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4989 · Cited by 1,040
“It is thought that regulated generation of the sIL-6R occurs through shedding rather than through differential splicing [16].”
BackgroundSelf-citation
Metadata
- Authors
- Dimitrov, S., Lange, T., Benedict, C., Nowell, M. A., Jones, S. A., Scheller, J., Rose‐John, S., Born, J., Dimitrov, S., Lange, T., Benedict, C., Nowell, M. A., Jones, S. A., Scheller, J., Rose‐John, S., & Born, J.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2006-08-15
- Volume
- 20
- Issue
- 12
- Pages
- 2174-2176
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2089623849
- Semantic Scholar
- f57ab1a45668acdae5874b167770f0412c77ec30
- Cited by
- 115
- References
- 61
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 2 · 2022: 11 · 2021: 8 · 2020: 3 · 2019: 8 · 2018: 4 · 2017: 6 · 2016: 5 · 2015: 9 · 2014: 7 · 2013: 6 · 2012: 6
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep, interleukin-6, IL-6 trans-signaling, soluble IL-6 receptor, soluble gp130, sleep-wake cycle, cytokine signaling, sleep-immune interaction
- MeSH terms
- Adult, Humans, Male, Monocytes, Sleep, Solubility, Tissue Distribution, Signal Transduction, Interleukin-6, Cytokines, Receptors, Interleukin-6
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
