Cytokines and Sleep Regulation

Krueger, James M.; Churchill, Lynn

doi:10.1007/978-1-4615-0323-1_8

Cited by 10 publications

(8 citation statements)

References 86 publications

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“…This variability could not be used to predict basic electrophysiological characteristics nor responses to SCN stimulation. An interesting feature of these VLPO neurons was that some dendrites appear to reach the ventral surface of the brain, suggesting that these neurons might detect substances distributed through the CSF, including those implicated in sleep regulation, such as cytokines, brain lipids and adenosine (Krueger & Fang, 1999). Similar observations have been reported for cortically projecting basal forebrain neurons (Semba et al, 1987), which are implicated in regulation of cortical activation.…”

Section: Characterization and Identi®cation Of Recorded Neuronssupporting

confidence: 67%

Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat

Sun

Whitefield

Rusak

et al. 2001

Eur J of Neuroscience

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The circadian pacemaker housed in the suprachiasmatic nucleus (SCN) synchronizes daily sleep-wake cycles, presumably by modulating the sleep-wake regulatory system, including ventrolateral preoptic area (VLPO) neurons. We used whole-cell patch-clamp recording to study the projections from the SCN to the VLPO in horizontal slices of rat hypothalamus. Single-pulse stimulation of the SCN region elicited postsynaptic currents (PSCs) in 20 of 66 neurons (30%) recorded within the VLPO region as verified by intracellular biocytin labelling. At a holding potential of -60 mV, the evoked PSCs had an amplitude of 17.6 +/- 3.2 pA (SEM) and a latency of 6.3 +/- 0.5 ms (n = 10). There was a trend for simple excitatory postsynaptic currents (EPSCs) to be evoked in the VLPO cluster, simple inhibitory postsynaptic currents (IPSCs) in the extended VLPO, and a combination of EPSCs and IPSCs in both regions. IPSCs were blocked reversibly by bicuculline (10 microm, n = 11). In both the presence and absence of bicuculline, EPSCs had fast and slow components that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microm; n = 7), and (+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 microm, n = 6), respectively. Reversal potentials for the evoked IPSCs and EPSCs were consistent with mediation via GABAA and ionotropic glutamate receptors, respectively. These results suggest that the SCN region provides both inhibitory and excitatory inputs to single VLPO neurons, which are mediated, respectively, by GABAA receptors and by both non-NMDA and NMDA glutamate receptors. These projections may play important roles in conveying circadian input to systems in the preoptic area that regulate sleep and waking.

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Section: Characterization and Identi®cation Of Recorded Neuronssupporting

confidence: 67%

Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat

Sun

Whitefield

Rusak

et al. 2001

Eur J of Neuroscience

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“…As already mentioned and reviewed in detail earlier, 8 there is convincing evidence in animals that inflammatory cytokines, in particular IL‐1β and TNF‐α, are the most important mediators of the increased amount and intensity of nonREM sleep during infections. A major role of these immune mediators in human sleep responses to infection is very probable, too, although the mechanisms are likely to be not identical.…”

Section: Mechanisms Underlying the Effects Of Immunomodulation On Slementioning

confidence: 67%

“…For unknown reasons rats and rabbits typically do not show reductions in nonREM sleep amount and increased wakefulness during infections or comparable experimental conditions that induce fever. 7,8 The increase in rectal temperature by itself cannot explain nonREM sleep suppression in humans, because passive body heating has opposite effects. 33,34 In our view, the most probable explanation at present is that HPA system activation, which becomes very prominent only in the febrile host response range, causes disturbed sleep through central CRH release, well known to suppress nonREM sleep.…”

Section: Mechanisms Underlying the Effects Of Immunomodulation On Slementioning

confidence: 99%

“…Therefore, it has been generally concluded that infections increase the amount and intensity of nonREM sleep in animals. Further studies revealed that the key mediators of infection‐induced alterations in sleep‐wake behavior are cytokines, 8 which are well known for the induction of other adaptive changes in CNS functions such as fever 9 and activation of the hypothalamic‐pituitary‐adrenal (HPA) system. 10 In particular the proinflammatory cytokines interleukin‐1 (IL‐1) and tumor necrosis factor‐α (TNF‐α) both increase nonREM sleep amount and intensity, and these effects can be blocked by specific antibodies or by endogenous antagonists of cytokine actions such as IL‐1 receptor antagonist 11 or soluble TNF receptor [sTNF‐R] p55.…”

Section: Introductionmentioning

confidence: 99%

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Experimental Immunomodulation, Sleep, and Sleepiness in Humans

Pollmächer

Schuld

Kraus

et al. 2000

Annals of the New York Academy of Sciences

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A BSTRACT : Infection, inflammation, and autoimmune processes are accompanied by serious disturbances of well-being, psychosocial functioning, cognitive performance, and behavior. Here we review those studies that have investigated the effects of experimental immunomodulation on sleep and sleepiness in humans. In most of these studies bacterial endotoxin was injected intravenously to model numerous aspects of infection including the release of inflammatory cytokines. These studies show that human sleep-wake behavior is very sensitive to host defense activation. Small amounts of endotoxin, which affect neither body temperature nor neuroendocrine systems but slightly stimulate the secretion of inflammatory cytokines, promote non-rapid-eye-movement sleep amount and intensity. Febrile host responses, in contrast, go along with prominent sleep disturbances. According to present knowledge tumor necrosis factor-␣ (TNF-␣ ) is most probably a key mediator of these effects, although it is likely that disturbed sleep during febrile host responses involves endocrine systems as well. There is preliminary evidence from human studies suggesting that inflammatory cytokines such as TNF-␣ not only mediate altered sleep-wake behavior during infections, but in addition are involved in physiological sleep regulation and in hypnotic effects of established sedating drugs.

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“…Both IL1 and TNF seem to be key components of the physiological sleep homeostat Krueger et al, 1995;Krueger and Obal, 1997;Vitkovic et al, 2000;Obal and Krueger, 2003). Consistent with current results, they affect each other's production and inhibition of one attenuates the sleep induced by the other (Takahashi et al, 1999.…”

Section: Discussionmentioning

confidence: 99%

Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

Taishi

Churchill

et al. 2008

Brain Research

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Hypothalamic and cortical mRNA levels for cytokines such as interleukin-1α (IL1α), tumor necrosis factor alpha (TNFα), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are impacted by systemic treatments of IL1β and TNFα To investigate the time course of the effects of IL1β and TNFα on hypothalamic and cortical cytokine gene expression, we measured mRNA levels for IL1β, TNFα, interleukin-6 (IL-6), interleukin-10 (IL-10), IL1 receptor 1, BDNF, NGF, and glutamate decarboxylase-67 in vitro using hypothalamic and cortical primary cultures. IL1β and TNFα mRNA levels increased significantly in a dose-dependent fashion after exposure to either IL1β or TNFα. IL1β increased IL1β mRNA in both the hypothalamic and cortical cultures after 2-6 h while TNFα mRNA increased significantly within 30 min and continued to rise up to 2-6 h. Most of the other mRNAs showed significant changes independent of dose in vitro. In vivo, intracerebroventricular (icv) injection of IL1β or TNFα also significantly increased IL1β, TNFα and IL6 mRNA levels in the hypothalamus and cortex. IL1β icv, but not TNFα increased NGF mRNA levels in both these areas. Results support the hypothesis that centrally active doses of IL1β and TNFα enhance their own mRNA levels as well as affect mRNA levels for other neuronal growth factors.

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Cytokines and Sleep Regulation

Cited by 10 publications

References 86 publications

Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat

Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat

Experimental Immunomodulation, Sleep, and Sleepiness in Humans

Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

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