Microbial Products and Cytokines in Sleep and Fever Regulation
Abstract
Excessive sleepiness and fever are constitutional symptoms associated with systemic infection. Although fevers have been investigated for many years, sleep responses to infectious challenge have only recently been investigated. Inoculation of animals with bacterial, viral, protozoan and fungal organisms result in complex sleep responses dependent upon the microbial agent and route of administration. The general pattern is characterized by an initial robust increase in non-rapid eye movement sleep (NREMS) followed by a period of NREMS inhibition. REMS is inhibited after infectious challenge. The sleep responses are accompanied by fever but the two responses are, in part, independent from each other. Sleep responses, like fevers, may be beneficial to host defense although this area is relatively uninvestigated. Microbial products likely responsible for sleep and fever responses include bacterial muramyl peptides and endotoxin, and viral double stranded RNA. These microbial products induce sleep and fever responses in animal models. The exact mechanism of how these structurally diverse microbial products elicit sleep and fever remain unknown; however these substances share the ability to induce cytokine production. Cytokines such as interleukin-1 (IL-1), tumor necrosis factor, acidic fibroblast growth factor (FGF), and interferon-alpha (IFN-alpha) are somnogenic whether given directly into brain or intravenously. Other cytokines lack somnogenic activity, e.g., IL-2, IL-6, IFN beta and basic FGF. The somnogenic actions of cytokines probably involve growth hormone-releasing hormone (GHRH) and nitric oxide. Anti-GHRH or inhibition of NO production inhibits normal sleep and inhibits IL-1-induced sleep. In conclusion, cytokines are likely key mediators of fever and sleep responses to infection. The microbial-cytokine altered sleep likely results from an amplification of physiological sleep mechanisms which include cytokines, several neuropeptides and neurotransmitters such as nitric oxide.
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SWS-dependent processes might actively counteract inflammation in the brain.
“SWS-dependent processes might actively counteract inflammation in the brain”
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Kronfol, Z., & Remick, D. G. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.5.683 · Cited by 784 · see citing works
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BackgroundCytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity
Dantzer, R. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.07.040 · Cited by 743 · see citing works
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Imeri, L., & Opp, M. R. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2576 · Cited by 710 · see citing works
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Basheer, R., Strecker, R. E., Thakkar, M. M., & McCarley, R. W. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.06.004 · Cited by 589 · see citing works
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Bryant, P. A., Trinder, J., & Curtis, N. (2004) · Nature Reviews Immunology · doi:10.1038/nri1369 · Cited by 551 · see citing works
“Inflammatory” Cytokines: Neuromodulators in Normal Brain?
Vitkovic, L., Bockaert, J., & Jacque, C. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.740457.x · Cited by 506 · see citing works
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Krueger, J. M., Obál, F., Fang, J., Kubota, T., & Taishi, P. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb05826.x · Cited by 423 · see citing works
Self-citationEffects of cytokines and infections on brain neurochemistry
Dunn, A. J. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.04.002 · Cited by 336 · see citing works
“However, IL-1 increases the duration of slow-wave sleep [208], whereas by far the most common sleep abnormality in depressed patients is insomnia.”
Behavioral Effects of Cytokines
Larson, S. J., & Dunn, A. J. (2001) · Brain Behavior and Immunity · doi:10.1006/brbi.2001.0643 · Cited by 295 · see citing works
Neumann, H., Schmidt, H., Cavalié, A., Jenne, D. E., & Wekerle, H. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.2.305 · Cited by 288 · see citing works
Sleep Neurobiology from a Clinical Perspective
España, R. A., & Scammell, T. E. (2011) · SLEEP · doi:10.5665/sleep.1112 · Cited by 282 · see citing works
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 · see citing works
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Koob, G. F., & Colrain, I. M. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0446-0 · Cited by 280 · see citing works
The neuroscience and endocrinology of fibromyalgia
Pillemer, S. R., Bradley, L. A., Crofford, L. J., Moldofsky, H., & Chrousos, G. P. (1997) · Arthritis & Rheumatism · doi:10.1002/art.1780401103 · Cited by 228 · 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
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Dantzer, R., Wollman, E. E., Vitković, L., & Yirmiya, R. (1999) · Advances in experimental medicine and biology · doi:10.1007/978-0-585-37970-8_17 · Cited by 220 · see citing works
Cytokines, “depression due to a general medical condition”, and antidepressant drugs
Yirmiya, R., Weidenfeld, J., Pollak, Y., Morag, M., Morag, A., Avitsur, R., Barak, O., Reichenberg, A., Cohen, E., Shavit, Y., et al. (1999) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-585-37970-8_16 · Cited by 208 · see citing works
Someren, E. J. W. V. (2002) · Ageing Research Reviews · doi:10.1016/s1568-1637(02)00030-2 · Cited by 195 · see citing works
Hansen, M. K., Taishi, P., Chen, Z., & Krueger, J. M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-06-02247.1998 · Cited by 193 · see citing works
Self-citationAnorexia of infection: current prospects
Langhans, W. (2000) · Nutrition · doi:10.1016/s0899-9007(00)00421-4 · Cited by 183 · see citing works
Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation
Romanovsky, A. A., & Székely, M. (1998) · Medical Hypotheses · doi:10.1016/s0306-9877(98)90022-6 · Cited by 173 · see citing works
Neural Substrate of Cold-Seeking Behavior in Endotoxin Shock
Almeida, M. C., Steiner, A. A., Branco, L. G. S., & Romanovsky, A. A. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000001 · Cited by 165 · see citing works
“, the energy-saving symptoms proposed or demonstrated to be beneficial during infection and severe inflammation [9–11].”
BackgroundHumoral 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 · see citing works
Self-citationDunlop, R., & Campbell, C. W. (2000) · Journal of Pain and Symptom Management · doi:10.1016/s0885-3924(00)00199-8 · Cited by 160 · see citing works
Effects of interleukin-1β on sleep are mediated by the type I receptor
Fang, J., Wang, Y., & Krueger, J. M. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.3.r655 · Cited by 152 · see citing works
Self-citationLorton, D., Lubahn, C. L., Estus, C., Millar, B. A., Carter, J. L., Wood, C. A., & Bellinger, D. L. (2006) · NeuroImmunoModulation · doi:10.1159/000104864 · Cited by 147 · see citing works
Deterioration of Spatial Learning Performances in Lipopolysaccharide-Treated Mice
Arai, K., Matsuki, N., Ikegaya, Y., & Nishiyama, N. (2001) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.87.195 · Cited by 145 · see citing works
Fever and hypothermia in systemic inflammation
Garami, A., Steiner, A. A., & Romanovsky, A. A. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64074-1.00034-3 · Cited by 148 · see citing works
Cytokines in immune function and sleep regulation
Krueger, J. M., Majde, J. A., & Rector, D. M. (2010) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52006-7.00015-0 · Cited by 133 · see citing works
“Further, sleep loss affects a variety of immune parameters, e.g., the ability of leukocytes to produce IFN (Krueger and Majde, 1994).”
InfluentialSelf-citationDiurnal variations of interleukin-1β mRNA and β-actin mRNA in rat brain
Taishi, P., Bredow, S., Guha‐Thakurta, N., Obál, F., & Krueger, J. M. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00002-7 · Cited by 132 · see citing works
Self-citationSickness behavior, its mechanisms and significance
Tizard, I. R. (2008) · Animal Health Research Reviews · doi:10.1017/s1466252308001448 · Cited by 129 · see citing works
“It is significant that minor increases in ambient temperature or low doses of microbial products also increase the amplitude of these slow waves (Krueger and Madje, 1994).”
BackgroundMartin, R. J., & Banks-Schlegel, S. P. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.158.3.9712132 · Cited by 121 · see citing works
Raison, C. L., Rye, D. B., Woolwine, B. J., Vogt, G. J., Bautista, B. M., Spivey, J. R., & Miller, A. H. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.019 · Cited by 116 · see citing works
Cancer Chemotherapy-Related Symptoms: Evidence to Suggest a Role for Proinflammatory Cytokines
Wood, L. J., Nail, L. M., Gilster, A., Winters, K. A., & Elsea, C. R. (2006) · Oncology nursing forum · doi:10.1188/06.onf.535-542 · Cited by 117 · see citing works
“Animal studies have shown that LPS promotes sleep disturbance by enhancing time spent in non–rapid-eye-movement sleep (Krueger, Obal, Fang, Kubota, & Taishi, 2001) through the action of IL-1 (cid:69) and TNF-(cid:68) (Krueger & Majde, 1994).”
BackgroundSleep/Wake Patterns of Individuals With Advanced Cancer Measured by Ambulatory Polysomnography
Parker, K. P., Bliwise, D. L., Ribeiro, M. H. L., Jain, S. R., Vena, C. I., Kohles-Baker, M. K., Rogatko, A., Xu, Z., & Harris, W. B. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.2135 · Cited by 116 · see citing works
Watkins, L. R., Hansen, M. K., Nguyen, K. T., Lee, J. E., & Maier, S. F. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00095-8 · Cited by 114 · see citing works
Viral Double-Stranded RNA, Cytokines, and the Flu
Majde, J. A. (2000) · Journal of Interferon & Cytokine Research · doi:10.1089/107999000312397 · Cited by 113 · see citing works
“Essentially all known proinflammatory cytokines and chemokines are induced by poly[rI rC], (45–48) by low molecular weight dsRNA (309 bp) of mixed base composition, (12) and presumably by comparable virus-associated dsRNA capable of inducing an APR. (29,49) Early gene induction by poly[rI ? rC],…”
Self-citationVena, C. I., Parker, K. P., Cunningham, M., Clark, J. R., & McMillan, S. (2004) · Oncology nursing forum · doi:10.1188/04.onf.735-746 · Cited by 114 · see citing works
Ram, A., Pandey, H. P., Matsumura, H., Kasahara-Orita, K., Nakajima, T., Takahata, R., Satoh, S., Terao, A., & Hayaishi, O. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01401-1 · Cited by 112 · see citing works
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 · see citing works
“IL-1 and TNF, as well as their receptors and other associated family members, are constitutively expressed in the brain (reviewed in Krueger and Majde 1994; Krueger and Oba l 1997).”
BackgroundInfluentialInvolvement of adenosine A2A receptor in sleep promotion
Satoh, S., Matsumura, H., & Hayaishi, O. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00302-1 · Cited by 105 · see citing works
Invited review: MDP and other muropeptides — direct and synergistic effects on the immune system
Traub, S., von Aulock, S., Härtung, T., & Hermann, C. (2006) · Journal of Endotoxin Research · doi:10.1179/096805106x89044 · Cited by 115 · 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
The Hypothalamic-Pituitary-Adrenal Axis and Viral Infection
Bailey, M. T., Engler, H., Hunzeker, J., & Sheridan, J. F. (2003) · Viral Immunology · doi:10.1089/088282403322017884 · Cited by 100 · see citing works
“For example, injecting mice with IL-1 b dose-dependently increases the amount of time spent in non-REM sleep (98,167).”
Hansen, M. K., Nguyen, K. T., Fleshner, M., Goehler, L. E., Gaykema, R. P. A., Maier, S. F., & Watkins, L. R. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.2.r331 · Cited by 101 · see citing works
“It is generally thought that in response to an infection, cytokines are released and are important mediators in signaling the central nervous system (CNS) to elicit ‘‘sickness behavior,’’ which includes fever, increases in sleep, depression in food-motivated behavior, exaggerated pain responses, and activation of the…”
BackgroundKrueger, 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
Self-citationYamamura, S., Morishima, H., Kumano‐go, T., Suganuma, N., Matsumoto, H., Adachi, H., Shigedo, Y., Mikami, A., Kai, T., Masuyama, A., et al. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602898 · Cited by 97 · see citing works
“Muramyl peptide is a cell-wall-derived substance that stimulates host defense systems, causes fever and has a somnogenic function (Krueger and Majde, 1994).”
BackgroundBasheer, R., Rainnie, D. G., Porkka‐Heiskanen, T., Ramesh, V., & McCarley, R. W. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00111-7 · Cited by 93 · see citing works
“In the present report, we have investigated the e¡ects of sleep deprivation on another transcription factor, NF-UB, as it is known to regulate the expression of several sleep modulatory substances, such as interleukin-1L (Borbe«ly and Tobler, 1989; Krueger and Majde, 1994; Opp and Krueger, 1991; Terao et al., 1998), t…”
BackgroundOpp, M. R., & Toth, L. A. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00010-1 · Cited by 93 · see citing works
Bacterial products and the control of ingestive behavior: Clinical implications
Langhans, W. (1996) · Nutrition · doi:10.1016/s0899-9007(96)80052-9 · Cited by 92 · see citing works
Brain Neurotransmission during Peripheral Inflammationa
Linthorst, A. C. E., & Reul, J. M. H. M. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09558.x · Cited by 88 · see citing works
Alt, J. A., Smith, T. L., Schlosser, R. J., Mace, J. C., & Soler, Z. M. (2014) · International Forum of Allergy & Rhinology · doi:10.1002/alr.21364 · Cited by 86 · see citing works
Sleep-Associated Changes in Interleukin-1β mRNA in the Brain
TAISHI, P., CHEN, Z., OBÁL, F., HANSEN, M. K., ZHANG, J., FANG, J., & KRUEGER, J. M. (1998) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.1998.18.793 · Cited by 88 · see citing works
“13).”
Self-citationBehavioral and psychological effects of immune activation
Yirmiya, R. (1997) · Current Opinion in Psychiatry · doi:10.1097/00001504-199711000-00011 · Cited by 88 · see citing works
Somnogenic relationships between tumor necrosis factor and interleukin-1
Takahashi, S., Kapás, L., Fang, J., & Krueger, J. M. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.4.r1132 · Cited by 87 · see citing works
Self-citationNitric Oxide Donors SIN-1 and SNAP Promote Nonrapid-Eye-Movement Sleep in Rats
Kapás, L., & Krueger, J. M. (1996) · Brain Research Bulletin · doi:10.1016/s0361-9230(96)00227-4 · Cited by 86 · see citing works
Self-citationNuclear factor-κB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep
Kubota, T., Kushikata, T., Fang, J., & Krueger, J. M. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.2.r404 · Cited by 83 · see citing works
Self-citationNuclear factor-κB-like activity increases in murine cerebral cortex after sleep deprivation
Chen, Z., Gardi, J., Kushikata, T., Fang, J., & Krueger, J. M. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.6.r1812 · Cited by 78 · see citing works
Self-citationHuman physiological models of insomnia
Richardson, G. S. (2007) · Sleep Medicine · doi:10.1016/s1389-9457(08)70003-0 · Cited by 74 · see citing works
“Another closely-related example is that of the cytokine network, which alters sleep–wake state in response to an infectious challenge.[15] Several lines of evidence suggest a role for abnormal stress regulation and, more specifically, for abnormal HPA axis function, in PI.”
BackgroundEffects of vagotomy on lipopolysaccharide-induced brain interleukin-1β protein in rats
Hansen, M. K., Nguyen, K. T., Goehler, L. E., Gaykema, R. P. A., Fleshner, M., Maier, S. F., & Watkins, L. R. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00230-7 · Cited by 74 · see citing works
Behavioral aspects of experimental autoimmune encephalomyelitis
Pollak, Y., Ovadia, H., Goshen, I., Gurevich, R., Monsa, K., Avitsur, R., & Yirmiya, R. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00257-x · Cited by 74 · see citing works
Wann, B. P., Bah, T. M., Kaloustian, S., Boucher, M., Dufort, A., Marec, N. L., Godbout, R., & Rousseau, G. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108089820 · Cited by 73 · see citing works
“These include decreased sleep, decreased exploratory behaviour, decreased social and sexual behaviour, impaired learning and memory (Krueger and Majde, 1994; Yirmiya, 1996; Nestler, et al., 2002a).”
BackgroundAvitsur, R., Pollak, Y., & Yirmiya, R. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00927-x · Cited by 73 · see citing works
Ilyin, S. E., Gayle, D. A., Flynn, M. C., & Plata‐Saláman, C. R. (1998) · Brain Research Bulletin · doi:10.1016/s0361-9230(97)00437-1 · Cited by 71 · see citing works
Kapás, L., Hansen, M. K., Chang, H.-Y., & Krueger, J. M. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.2.r406 · Cited by 70 · see citing works
“SYSTEMIC INFECTIONS, peripheral lipopolysaccharide (LPS) treatments, and several cytokines all induce central nervous system-related symptoms of the acute phase response, such as increased non-rapid eye movement sleep (NREMS) and fever (21).”
BackgroundSelf-citationTerao, A., Matsumura, H., & Saito, M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-16-06599.1998 · Cited by 69 · see citing works
“, 1984) (for review, see Borbély and Tobler, 1989; Krueger and Majde, 1994); (2) inhibition of endogenous IL-1 by an IL-1 receptor antagonist (Opp and Krueger, 1991) and by anti-IL-1 antibodies (Opp and Krueger, 1994) inhibited the occurrence of spontaneous sleep in rabbits; (3) anti-IL-1 antibodies suppressed the sle…”
BackgroundHypothalamic Regulation of Sleep
Salín-Pascual, R. J. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00318-9 · Cited by 71 · see citing works
Irwin, M. R., Straub, R. H., & Smith, M. T. (2023) · Nature Reviews Rheumatology · doi:10.1038/s41584-023-00997-3 · Cited by 76 · see citing works
Interleukin-10 Inhibits Spontaneous Sleep in Rabbits
Kushikata, T., Fang, J., & Krueger, J. M. (1999) · Journal of Interferon & Cytokine Research · doi:10.1089/107999099313244 · Cited by 69 · see citing works
Self-citationRaison, C. L., & Miller, A. H. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.194 · Cited by 68 · see citing works
“Hypersom-nia has been recognized for years as a primary behavioral manifestation of proinflammatory cytokines (Krueger and Majde, 1994; Krueger and Toth, 1994; Krueger and Majde, 2003; Opp, 2004, 2009), and studies in healthy adolescents and adults indicate that chronically increased sleep is…”
Central/peripheral nervous system and immune responses
Lawrence, D. A. (2000) · Toxicology · doi:10.1016/s0300-483x(99)00144-4 · Cited by 67 · see citing works
Szentirmai, É., Massie, A. R., & Kapás, L. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.12.008 · Cited by 67 · see citing works
Effects of Interleukin-1 on Sexual Attractivity in a Model of Sickness Behavior
Avitsur, R., Cohen, E., & Yirmiya, R. (1997) · Physiology & Behavior · doi:10.1016/s0031-9384(97)00381-8 · Cited by 62 · see citing works
Krueger, J. M., & Takahashi, S. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb51706.x · Cited by 61 · see citing works
Self-citationKrueger, J. M., Majde, J. A., & Obál, F. (2003) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00065-x · Cited by 61 · see citing works
Self-citationInterleukin-4 inhibits spontaneous sleep in rabbits
Kushikata, T., Fang, J., Wang, Y., & Krueger, J. M. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.4.r1185 · Cited by 60 · see citing works
Self-citationEffects of Muramyl Peptides on Macrophages, Monokines, and Sleep
Pabst, M. J., Beranová-Giorgianni, Š., & Krueger, J. M. (1999) · NeuroImmunoModulation · doi:10.1159/000026384 · Cited by 58 · see citing works
Self-citationNadjar, A., Wigren, H., & Tremblay, M. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00250 · Cited by 56 · see citing works
“Many pathogens comprising gram-positive and gramnegative bacteria (Toth and Krueger, 1988, 1989; Krueger and Majde, 1994), viruses (influenza virus, rhinovirus, and human immunodeficiency virus) (Norman et al., 1988, 1990; Toth et al., 1995; Opp et al., 1996; Gemma and Opp, 1999), fungal organisms…”
BackgroundMajde, J. A., Guha‐Thakurta, N., Chen, Z., et al. (1998) · Archives of Virology · doi:10.1007/s007050050467 · Cited by 57 · see citing works
“In recent years it has become apparent that the constitutional symptoms associated with bacterial infections are mediated primarily by proinflammatory cytokines induced by bacterial constituents [5].”
InfluentialSelf-citationRehman, A., Taishi, P., Fang, J., Majde, J. A., & Krueger, J. M. (2001) · Cytokine · doi:10.1006/cyto.2000.0800 · Cited by 55 · see citing works
Self-citationBehavioral and Motivational Effects of Immune-System Activation
Larson, S. J. (2002) · The Journal of General Psychology · doi:10.1080/00221300209602104 · Cited by 55 · see citing works
Sleep as a window on the developing brain
Kohyama, J. (1998) · Current Problems in Pediatrics · doi:10.1016/s0045-9380(98)80054-6 · Cited by 56 · see citing works
Cytokine-Neurotransmitter Interactions in the Brain
Simoni, M. G. D., & Imeri, L. (1998) · Neurosignals · doi:10.1159/000014526 · Cited by 55 · see citing works
Krueger, J. M., Fang, J., Hansen, M. K., Zhang, J., & Obál, F. (1998) · Physiology · doi:10.1152/physiologyonline.1998.13.4.189 · Cited by 51 · see citing works
“This list includes the cytokines, interleukin-1 (IL-1) (9,10) and tumor necrosis factor (TNF) (4), and growth hormone (GH)-releasing hormone (GHRH) (11,12), prostaglandin D2 (5), and adenosine (6) for NREMS and prolactin (PRL) (14), vasoactive intestinal peptide (VIP) (3,7), and corticotropin-like intermediate lobe pe…”
BackgroundSelf-citationClement, H. W., Buschmann, J., Rex, S., Grote, C., Opper, C., Gemsa, D., & Wesemann, W. (1997) · Journal of Neural Transmission · doi:10.1007/bf01273312 · Cited by 50 · see citing works
Wieczorek, M., & Dunn, A. J. (2006) · Brain Research · doi:10.1016/j.brainres.2006.04.120 · Cited by 48 · see citing works
“IL-1 also induces characteristic behavioral changes, including decreases in locomotor activity, exploration, feeding and sexual activity (Dantzer et al., 2001;Larson and Dunn, 2001) and increases the time spent in slow-wave sleep (Krueger and Majde, 1995).”
BackgroundTavares, E., Maldonado, R., Ojeda, M. L., & Miñano, F. J. (2005) · Clinical and Vaccine Immunology · doi:10.1128/cdli.12.9.1085-1093.2005 · Cited by 48 · see citing works
“ized by fever and the production of cytokines in vitro and in vivo (9, 20, 30), with cells and animals being more sensitive to LPS than to MDP (42).”
BackgroundGrowth Hormone, Fatigue, Poor Sleep, and Disability in HIV Infection
Darko, D. F., Mitler, M. M., & Miller, J. C. (1998) · Neuroendocrinology · doi:10.1159/000054329 · Cited by 47 · see citing works
Meusel, T. R., Kehoe, K. E., & Imani, F. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.12.6429 · Cited by 47 · see citing works
“dsRNA has been shown to induce several cytokines including TNF- and IL-1 in monocytic cell lines (20, 21).”
BackgroundEndoscopic sinus surgery improves cognitive dysfunction in patients with chronic rhinosinusitis
Alt, J. A., Mace, J. C., Smith, T. L., & Soler, Z. M. (2016) · International Forum of Allergy & Rhinology · doi:10.1002/alr.21820 · Cited by 46 · see citing works
Saber, M., Giordano, K. R., Hur, Y., Ortiz, J. B., Morrison, H., Godbout, J. P., Murphy, S. M., Lifshitz, J., & Rowe, R. K. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14611 · Cited by 46 · see citing works
Effects of Sleep on Endotoxin-Induced Host Responses in Healthy Men
Haack, M., Schuld, A., Kraus, T., & Pollmächer, T. (2001) · Psychosomatic Medicine · doi:10.1097/00006842-200107000-00008 · Cited by 44 · see citing works
“The injection time points of placebo and endotoxin in the sleep group (5 minutes after initiation of stable SWS) were 2341 hours 6 13 minutes (range 2325– 0005 hours) and 2349 hours 6 18 minutes (range 2317–0017 hours), respectively (F(1,9) 5 3.”
BackgroundInfluentialBiological properties of bacterial peptidoglycan
Johannsen, L. (1993) · Apmis · doi:10.1111/j.1699-0463.1993.tb00119.x · Cited by 44 · see citing works
Spontaneous, homeostatic, and inflammation-induced sleep in NF-κB p50 knockout mice
Jhaveri, K. A., Ramkumar, V., Trammell, R. A., & Toth, L. A. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00262.2006 · Cited by 40 · see citing works
“LPS also activates NF- B (46), which in turn promotes the production of TNF- , IL-1 , and NOS (16, 62).”
BackgroundInfluentialA Review of Sleep in Selected Immune and Autoimmune Disorders
Lashley, F. R. (2003) · Holistic Nursing Practice · doi:10.1097/00004650-200303000-00002 · Cited by 47 · see citing works
Henriksen, S. J., Prospero-Garcia, O. E., Phillips, T. R., et al. (1995) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-79657-9_12 · Cited by 42 · see citing works
Schmidt, E.-M., Linz, B., Diekelmann, S., Besedovsky, L., Lange, T., & Born, J. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.11.012 · Cited by 41 · see citing works
“, 1982), the idea has been around for a long time that pro-inflammatory cytokines that are released in response to microbial challenge are involved in the homeostatic regulation of sleep, especially of slow wave sleep (SWS) (Krueger and Majde, 1994; Krueger et al., 1995).”
Background
- Authors
- Krueger, J. M., & Majde, J. A.
- Affiliations
- University of Tennessee Health Science Center (US)
- Office of Naval Research (US)
- Venue
- Critical Reviews™ in Immunology
- Publisher
- Begell House
- Published
- 1994
- Volume
- 14
- Issue
- 3-4
- Pages
- 355-379
- ISSN
- 0197-3355 (ISSN-L)
- 2162-6472
- OpenAlex
- W2024033128
- Cited by
- 213
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 1 · 2017: 4 · 2016: 4 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Reviews in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep regulation, fever regulation, cytokines, microbial products, infection, NREM sleep, REM sleep, interleukin-1, TNF-α, interferon-alpha, acidic fibroblast growth factor, growth hormone-releasing hormone, nitric oxide, muramyl peptides, endotoxin, double-stranded RNA, host defense
- MeSH terms
- Animals, Bacterial Proteins, Endotoxins, Fever, Humans, Models, Biological, RNA, Double-Stranded, Sleep, Viruses, Cytokines
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