Humoral Sleep Regulation; Interleukin-1 and Tumor Necrosis Factor

doi:10.1016/B978-0-12-394623-2.00013-5

Vitamins & Hormones

Volume 89, 2012, Pages 241-257

https://doi.org/10.1016/B978-0-12-394623-2.00013-5 Get rights and content

Abstract

Two substances, the cytokines interleukin-1 beta (IL1β) and tumor necrosis factor alpha (TNFα), known for their many physiological roles, for example, cognition, synaptic plasticity, and immune function, are also well characterized in their actions of sleep regulation. These substances promote non-rapid eye movement sleep and can induce symptoms associated with sleep loss such as sleepiness, fatigue, and poor cognition. IL1β and TNFα are released from glia in response to extracellular ATP. They bind to their receptors on neurons resulting in neuromodulator and neurotransmitter receptor up/downregulation (e.g., adenosine and glutamate receptors) leading to altered neuronal excitability and function, that is, a state change in the local network. Synchronization of state between local networks leads to emergent whole brain oscillations, such as sleep/wake cycles.

Introduction

Despite the importance of sleep to our everyday lives, its biochemical regulation continues to confound us. Many studies have provided strong evidence that sleep is regulated, in part, by humoral agents dubbed “sleep-regulatory substances” or SRSs (Borbély and Tobler, 1989, Imeri and Opp, 2009, Inoue, 1989, Jouvet, 1984, Kilduff and Peyron, 2000, Krueger, 2008, Krueger et al., 1990, Krueger et al., 2008, Obál et al., 2003, Roky et al., 1995). The first discovery of SRSs that accumulated in cerebrospinal fluid during prolonged waking occurred over a century ago (Ishimori, 1909, Legendre and Piéron, 1913).

To be classified as an SRS, a substance must meet several criteria (Borbély and Tobler, 1980, Imeri and Opp, 2009, Jouvet, 1984, Krueger and Obál, 1994). These include (1) the substance and/or its receptor changes with sleep propensity, (2) administration of the substance increases or decreases sleep, (3) blocking the action or inhibiting the production of the substance changes sleep, (4) levels of the substance change during disease states associated with altered sleep, for example, infection, and finally (5) the substance acts on known sleep-regulatory circuits. While there are many substances meeting some of these criteria, including microRNAs, metabolites, hormones, growth factors, transcription factors, and various proteins and their receptors, only a few meet all the required characteristics.

Section snippets

Interleukin-1β and Tumor Necrosis Factor α

Two well-characterized SRSs are the cytokines interleukin-1 beta (IL1β) and tumor necrosis factor alpha (TNFα). While well known for their contribution to signaling in the peripheral immune system, cytokines and their receptors are constitutively expressed in the central nervous system of healthy organisms, supporting the notion that they have functions beyond immune responses (Opp, 2005, Szelényi, 2001).

Electrophysiological, biochemical, and molecular genetic studies of IL1β and TNFα

Cytokine Production and Release

IL1β and TNFα mRNAs are detectable in various areas of the brain in several species (reviewed by Vitkovic et al., 2000). Because constitutive expression of IL1β (Medana et al., 1997, Taishi et al., 1997) and TNFα (Bredow et al., 1997) mRNAs is region specific and diurnal, some studies did not find them in normal rodent brains (reviewed by Vitkovic et al., 2000). IL1β protein is present in many areas in both neurons and glia in normal rat and mouse brains (Bandtlow et al., 1990, Hagan et al.,

Cytokines and Sleep

Cytokines have important roles in multiple physiological functions, including sleep regulation (Krueger et al., 2001), memory (Yirmiya and Goshen, 2011), appetite (Andréasson et al., 2007), cerebral circulation (Faraci and Heistad, 1998), temperature regulation (Leon, 2002), and insulin production (Fu et al., 2006). Several cytokines, including the proinflammatory cytokines IL1α, IL1β, IL6, IFNα, IFNγ, TNFα, and TNFβ, have the capacity to enhance NREMS (reviewed by Krueger and Majde, 2003,

Cytokines in Sleep Regulation

The dominant paradigm in sleep research posits that sleep is initiated and regulated by subcortical neuronal networks (reviewed in Szymusiak and McGinty, 2008).

The arousal systems, for example, the noradrenergic locus coeruleus, serotonergic dorsal raphe nucleus, cholinergic neurons in the basal forebrain, and histaminergic neurons in the tuberomammillary nucleus, provide activating inputs to the diencephalon, limbic system, and neocortex (Saper, 1987). The hypocretin (orexin) neurons in the

Acknowledgment

This work was supported by grants from the National Institutes of Health, NS025378, NS031453, and HD36520.

References (163)

A. Andréasson et al.
A putative role for cytokines in the impaired appetite in depression
Brain Behav. Immun.
(2007)
F. Baracchi et al.
Sleep-wake behavior and responses to sleep deprivation of mice lacking both interleukin-1beta receptor 1 and tumor necrosis factor-alpha receptor 1
Brain Behav. Immun.
(2008)
B.T. Baune et al.
Association between genetic variants of IL-1beta, IL-6 and TNF-alpha cytokines and cognitive performance in the elderly general population of the MEMO-study
Psychoneuroendocrinology
(2008)
A.A. Borbély et al.
The search for an endogenous sleep substances
TIPS
(1980)
S. Brandwein
Regulation of interleukin 1 production by mouse peritoneal macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferons
J. Biol. Chem.
(1986)
L. Churchill et al.
Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1β or tumor necrosis factor α
Brain Res.
(2006)
L. Churchill et al.
Tumor necrosis factor alpha: Activity dependent expression and promotion of cortical column sleep in rats
Neuroscience
(2008)
F. Colotta et al.
The type II “decoy” receptor: A novel regulatory pathway for interleukin 1
Immunol. Today
(1994)
A. Da Cunha et al.
Glial cell-specific mechanisms of TGF-beta 1 induction by IL-1 in cerebral cortex
J. Neuroimmunol.
(1993)
A. Da Cunha et al.
Control of astrocytosis by interleukin-1 and transforming growth factor-beta 1 in human brain
Brain Res.
(1993)

R. Dantzer

Cytokin-induced sickness behavior: A neuroimmune response to activation of innate immunity

Eur. J. Pharmacol.

(2004)

G. De Sarro et al.

Comparative, behavioural and electrocortical effects of tumor necrosis factor-alpha and interleukin-1 microinjected into the locus coeruleus of rat

Life Sci.

(1997)

T. Deak et al.

Stress-induced increases in hypothalamic IL-1: A systematic analysis of multiple stressor paradigms

Brain Res. Bull.

(2005)

C.A. Dinarello

Interleukin-1 and interleukin-1 antagonism

Blood

(1991)

C. Dinarello

Proinflammatory cytokines

Chest

(2000)

R.D. Fields et al.

ATP: An extracellular signaling molecule between neurons and glia

Trends Neurosci.

(2000)

K. Fitzgerald et al.

The role of the interleukin-1/Toll-like receptor superfamily in inflammation and host defence

Microbes Infect.

(2000)

D.J. Frey et al.

The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults

Brain Behav. Immun.

(2007)

R. Gibson et al.

CNS injury: The role of the cytokine IL-1

Vet. J.

(2004)

D.V. Goeddel

Signal transduction by tumor necrosis factor

Chest

(1999)

E. Granowitz et al.

Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: I. IL-1 receptor antagonist inhibits IL-1-induced cytokine synthesis and blocks the binding of IL-1 to its type II receptor on human monocytes

Blood

(1992)

M.M. Halassa et al.

Tripartite synapses: Roles for astrocyte purines in the control of synaptic physiology and behavior

Neuropharmacology

(2009)

M. Hristova et al.

Metabolic syndrome-neurotrophic hypothesis

Med. Hypotheses

(2006)

J. Hu et al.

Sleep-deprived mice show altered cytokine production manifest by perturbations in serum IL-1ra, TNFa, and IL-6 levels

Brain Behav. Immun.

(2003)

T. Ignatowski et al.

Neuronal-associated tumor necrosis factor (TNF alpha): Its role in noradrenergic functioning and modification of its expression following antidepressant drug administration

J. Neuroimmunol.

(1997)

J. Inoue et al.

Tumor necrosis factor receptor-associated factor (TRAF) family: Adapter protein that mediate cytokine signaling

Exp. Cell Res.

(2000)

T.S. Kilduff et al.

The hypocretin/orexin ligand-receptor system: Implications for sleep and sleep disorders

Trends Neurosci.

(2000)

J. Konsman et al.

Cytokine-induced sickness behavior: Mechanisms and implications

Trends Neurosci.

(2002)

K. Kristiansen et al.

Rhythmic electrical activity from isolated cerebral cortex

Electroencephalogr. Clin. Neurophysiol.

(1949)

J.M. Krueger et al.

Sleep and cytokines

Sleep Med. Clinics

(2007)

T. Kubota et al.

Intrapreoptic microinjection of TNF-alpha enhances non-REM sleep in rats

Brain Res.

(2002)

R. Lechan et al.

Immunoreactive interleukin-1β localization in the rat forebrain

Brain Res.

(1990)

O.I. Lyamin et al.

Unihemispheric slow wave sleep and the state of the eyes in a white whale

Behav. Brain Res.

(2002)

M.N. Alam et al.

Interleukin-1beta modulates state-dependent discharge activity of preoptic area and basal forebrain neurons: Role in sleep regulation

Eur. J. Neurosci.

(2004)

S. Allan et al.

Interleukin-1 and neuronal injury

Nat. Rev. Immunol.

(2005)

H. Anisman et al.

Cytokines, stress and depressive illness: Brain-immune interactions

Ann. Med.

(2003)

E. Atkins et al.

Studies on the pathogenesis of fever. I. The presence of transferable pyrogen in the blood stream following the injection of typhoid vaccine

J. Exp. Med.

(1955)

C. Bandtlow et al.

Regional and cellular codistribution of interleukin-1β and nerve growth factor mRNA in the adult rat brain: Possible relationship to the regulation of nerve growth factor synthesis

J. Cell Biol.

(1990)

S. Banks et al.

Behavioral and physiological consequences of sleep restriction

J. Clin. Sleep Med.

(2007)

H. Barksby et al.

The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders

Clin. Exp. Immunol.

(2007)

L. Bertazza et al.

Tumor necrosis factor (TNF) biology and cell death

Front. Biosci.

(2008)

F. Bianco et al.

Astrocyte-derived ATP induces vesicle shedding and IL-1β release from microglia

J. Immunol.

(2005)

A.A. Borbély et al.

Endogenous sleep-promoting substances and sleep regulation

Physiol. Rev.

(1989)

J. Bradley

TNF-mediated inflammatory disease

J. Pathol.

(2008)

C. Breder et al.

Distribution and characterization of tumor necrosis factor-alpha-like immunoreactivity in the murine central nervous system

J. Comp. Neurol.

(1993)

S. Bredow et al.

Diurnal variations of tumor necrosis factor alpha mRNA and alpha-tubulin mRNA in rat brain

Neuroimmunomodulation

(1997)

D. Brough et al.

Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death

J. Cell Sci.

(2007)

G. Burnstock

Purinergic signaling—An overview

Novartis Found. Symp.

(2006)

G. Burnstock

Physiology and pathophysiology of purinergic neurotransmission

Physiol. Rev.

(2007)

M.D. Carmichael et al.

Role of brain IL-1β on fatigue after exercise induced muscle damage

Am. J. Physiol. Regul. Integr. Comp. Physiol.

(2006)

Cited by (62)

A dopamine D1-like receptor-specific agonist improves the survival of septic mice
2024, iScience
In this study, a murine sepsis model was developed using the cecum ligation and puncture (CLP) technique. The expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in the brain increased 6 h after CLP but decreased 24 h later when elevated endogenous dopamine levels in the brain were sustained. Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride reduced dopamine levels in the striatum and increased mortality in septic mice. Dopamine D1-like receptors were significantly expressed in the brain, but not in the lungs. Intraperitoneally administered SKF-81297 (SKF), a blood-brain barrier-permeable D1-like receptor agonist, prevented CLP-induced death of septic mice with ameliorated acute lung injury and cognitive dysfunction and suppressed TNF-α and IL-1β expression. The D1-like receptor antagonist SCH-23390 abolished the anti-inflammatory effects of SKF. These data suggest that D1-like receptor-mediated signals in the brain prevent CLP-induced inflammation in both the brain and the periphery.
Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis
2024, ESMO Open
Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation.
This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined ‘cut-off’ ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to ‘early’ or ‘late’ ToD of ICIs were collected from each report and pooled.
Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups.
Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.
Battle royale: Immune response on biofilms – host-pathogen interactions
2023, Current Research in Immunology
The research interest of the scientific community in biofilm-forming microorganisms is growing due to the problems caused by their infections affecting humans and animals, mainly because of the difficulty of the host immune system in eradicating these microbial complex communities and the increasing antimicrobial resistance rates worldwide. This review describes the virulence factors and their interaction with the microbial communities of four well-known and highly biofilm-forming pathogens, more exactly, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus spp., and Candida spp. The innate and adaptive immune responses caused by the infection with these microorganisms and their evasion to the host immune system by biofilm formation are discussed in the present work. The relevance of the differences in the expression of certain virulence factors and the immune response in biofilm-associated infections when compared to planktonic infections is usually described as the biofilm architecture protects the pathogen and alters the host immune responses, here we extensively discussed these mechanisms.
Interactions between heavy metals and sleep duration among pre-and postmenopausal women: A current approach to molecular mechanisms involved
2023, Environmental Pollution
Citation Excerpt :
Gene Ontology (GO) terms including “type 1 melanocortin receptor binding”, “endocrine hormone secretion”, “interleukin-1 receptor antagonist activity”, “altered melanocortin system”, and “sleep wake disorders” were among the top 5 clustered enriched findings. Furthermore, five genes altered by heavy metals (IL1B, POMC, NFIL3, BHLHE40, HTR7) were found to be associated with sleep disorders in this study, which concurs with previous evidence (Hedlund, 2009; Jewett and Krueger, 2012; Pellegrino et al., 2014; Goldstein et al., 2018; Kubo, 2020). In particular, IL1B, POMC, and BHLHE40 were commonly altered genes induced by three heavy metals (cadmium, lead, and mercury).
The effects of heavy metals (cadmium, lead, and mercury) and their mixtures on sleep duration in pre-and postmenopausal women, particularly the molecular mechanisms, remain unknown. Here, we assessed the interaction between heavy metals and sleep duration among pre-and postmenopausal women (n = 1134). Furthermore, molecular mechanisms related to sleep disorders induced by studied heavy metals were further analyzed to support the previous findings. We found that serum lead levels were positively related to weekend and weekday sleep duration in premenopausal women. There were interactions between serum lead and mercury and menopausal status for sleep duration. Serum lead and mercury levels were shown to be inversely related to sleep duration in postmenopausal women. Despite the lack of statistically significant associations between mixed heavy metals and sleep duration, there were increasing trends in premenopausal women's sleeping patterns and decreasing trends in postmenopausal women's sleeping patterns. In silico analysis, IL1B, hsa-21-5p, hsa-887-3p, hsa-877-3p, and NR4A1 were identified as the most relevant genes, miRNAs, and transcription factors linked with sleep disorders induced by combined heavy metals (cadmium, lead, and mercury). Furthermore, “type 1 melanocortin receptor binding,” “endocrine hormone secretion,” “interleukin-1 receptor antagonist activity,” “altered melanocortin system,” and “sleep wake disorders” were identified as the predominant molecular mechanisms involved in the pathophysiology of sleep disorders induced by the studied heavy metals. Cut off point values and miRNA sponge templates for heavy metal exposure levels relevant to sleep disorders in pre- and postmenopausal women were reported. Future research is needed to verify our findings and provide insight into the molecular processes of long-term mixed heavy metal exposure in various populations, such as children and the elderly.
Sleepiness profiles in mice submitted to acute and chronic sleep deprivation
2022, Behavioural Processes
Sleepiness is a behavioural consequence of sleep pressure, which shows interindividual variation, a characteristic possibly related to central sleep mechanisms. However, there is a lack of evidence linking progressive sleep need and sleepiness with factors of individual variability, which could be tested by total acute and chronic sleep deprivation. Thus, the objective of the study was to investigate the development of sleepiness in sleep deprived mice. Male C57BL/6J mice were distributed in sleep deprivation, sleep rebound and control groups. Animals underwent acute sleep deprivation for 3, 6, 9 or 12 h or chronic sleep deprivation for 6 h for 5 consecutive days. Sleep rebound groups had a sleep opportunity for 1, 2, 3, or 4 h after acute sleep deprivation or 24 h after chronic sleep deprivation. During the protocols, sleep attempts were counted to calculate a sleepiness index. After euthanasia, blood was collected for corticosterone assessment. Using the average of group sleep attempts, it was possible to differentiate between sleepy (mean>group average) and resistant animals (mean<group average). Resistant mice were more frequent in all protocols. Individual variation accounted for 52% of sleepiness variance during chronic sleep deprivation and extended wakefulness explained 68% of sleepiness variance during acute sleep deprivation. A normal corticosterone peak was observed at the start of the dark phase, independent of sleep deprivation. Different profiles of sleepiness emerged in sleep deprived mice. Sleep deprivation was the main factor for sleepiness during acute sleep deprivation whereas in chronic deprivation individual variation was more relevant.
Traumatic brain injury: Inter-relationship with sleep
2022, Cellular, Molecular, Physiological, and Behavioral Aspects of Traumatic Brain Injury
Around 46%–72% of traumatic brain injury (TBI) survivors suffer from sleep disturbances, which can manifest acutely or chronically post-injury. This chapter will cover anatomy and causes of the acute and chronic sleep disturbances that are often seen in TBI survivors. On a gross anatomical scale, the main areas of the brain involved in sleep are various cortical regions, the hypothalamus, the basal forebrain, and the brainstem. Injury to these regions can lead to sleep disturbances post-TBI, including insomnia, sleep apnea, hypersomnia, day-time fatigue, narcolepsy, and restless-legs syndrome. Ultimately, sleep disturbances can exacerbate TBI-related pathologies, interfere with recovery and rehabilitation, and worsen the prognosis for patients. This happens because sleep is heavily involved in maintaining the cellular homeostasis of the brain. Disrupted sleep can offset the brain’s chemical balance and cause a wide range of problems including neuronal death. There are many factors that can influence this process, such as the brain areas affected, acute and chronic inflammation, severity of the TBI, age at injury, gender, and clinical interventions. Therefore, it is critical that we understand the bi-directional relationship between TBI and sleep, to promote the development of effective treatments and improve clinical outcomes for TBI patients.

View all citing articles on Scopus

View full text

Chapter Thirteen - Humoral Sleep Regulation; Interleukin-1 and Tumor Necrosis Factor

Abstract

Introduction

Section snippets

Interleukin-1β and Tumor Necrosis Factor α

Cytokine Production and Release

Cytokines and Sleep

Cytokines in Sleep Regulation

Acknowledgment

Brain Behav. Immun.

Brain Behav. Immun.

Psychoneuroendocrinology

TIPS

J. Biol. Chem.

Brain Res.

Neuroscience

Immunol. Today

J. Neuroimmunol.

Brain Res.

Eur. J. Pharmacol.

Life Sci.

Brain Res. Bull.

Blood

Chest

Trends Neurosci.

Microbes Infect.

Brain Behav. Immun.

Vet. J.

Chest

Blood

Neuropharmacology

Med. Hypotheses

Brain Behav. Immun.

J. Neuroimmunol.

Exp. Cell Res.

Trends Neurosci.

Trends Neurosci.

Electroencephalogr. Clin. Neurophysiol.

Sleep Med. Clinics

Brain Res.

Brain Res.

Behav. Brain Res.

Interleukin-1beta modulates state-dependent discharge activity of preoptic area and basal forebrain neurons: Role in sleep regulation

Eur. J. Neurosci.

Interleukin-1 and neuronal injury

Nat. Rev. Immunol.

Cytokines, stress and depressive illness: Brain-immune interactions

Ann. Med.

Studies on the pathogenesis of fever. I. The presence of transferable pyrogen in the blood stream following the injection of typhoid vaccine

J. Exp. Med.

Regional and cellular codistribution of interleukin-1β and nerve growth factor mRNA in the adult rat brain: Possible relationship to the regulation of nerve growth factor synthesis

J. Cell Biol.

Behavioral and physiological consequences of sleep restriction

J. Clin. Sleep Med.

The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders

Clin. Exp. Immunol.

Tumor necrosis factor (TNF) biology and cell death

Front. Biosci.

Astrocyte-derived ATP induces vesicle shedding and IL-1β release from microglia

J. Immunol.

Endogenous sleep-promoting substances and sleep regulation

Physiol. Rev.

TNF-mediated inflammatory disease

J. Pathol.

Distribution and characterization of tumor necrosis factor-alpha-like immunoreactivity in the murine central nervous system

J. Comp. Neurol.

Diurnal variations of tumor necrosis factor alpha mRNA and alpha-tubulin mRNA in rat brain

Neuroimmunomodulation

Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death

J. Cell Sci.

Purinergic signaling—An overview

Novartis Found. Symp.

Physiology and pathophysiology of purinergic neurotransmission

Physiol. Rev.

Role of brain IL-1β on fatigue after exercise induced muscle damage

Am. J. Physiol. Regul. Integr. Comp. Physiol.