Cytokines sleep

Mills PI, Dimsdale IE (2004) Sleep apnea a model for studying cytokines, sleep, and sleep disruption. Brain Behav Immun 18 298-303... 

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

These are generated by the liver during infections and other forms of inflammatory challenge, as part of the acute-phase response. This response to infection is characterised by fever, sleep, adrenotrophic hormone release, decreased plasma iron and zinc levels, elevated neutrophils in the bloodstream and enhanced cytokine production. These changes, part of the body s response to combat infection, occur within hours. The elevated temperatures may inhibit the replication of some bacteria and viruses and may also enhance the function of some immune cells. 

Proinflammatory cytokines, released by activated macrophages and monocytes during infection, can act on neural targets that control thermogenesis, behavior, and mood. In addition to induction of fever, cytokines induce other biological functions associated with the acute-phase response, including hypophagia and sleep. Cytokine production has been detected within the central nervous... 

It has been proposed that the changes in sleep-wake behavior during HIV infection may be due to an effect of the virus directly on the central nervous system (199,212). There is evidence that penetration of the blood-brain barrier by the virus occurs as early as the acute or clinical latency phase, prior to the development of symptoms (155). During the early stages of HIV infection, the sleep-promoting cytokines TNF-a and IL-ip are elevated relative to normal (199,212). It... 

Krueger JM, Johannsen L. Bacterial products, cytokines and sleep. J Rheumatol 1989 suppl 19 52-57. 

We are not certain which comorbid risk factors cause mortality independent of sleep effects, and therefore, we cannot be certain whether we controlled too much or too little for comorbidities. For example, since short sleep or long sleep may cause a person to be sick at present or to get little exercise or to have heart disease (17), diabetes (18), etc., controlling for these possible mediating variables may have incorrectly minimized the hazards associated with sleep durations. This would be overcontrol. The hazard ratios for participants who were rather healthy at the time of the initial questionnaires were unlikely to be overcontrolled for initial illness. Since the 32-covariate models and the hazard ratios for initially healthy participants were similar, this similarity reduced concern that the 32-covariate models were overcontrolled. On the other hand, there may have been residual confounding processes that caused both short or long sleep and early death that we could not adequately control in the CPSII data set, either because available control variables did not adequately measure the confound or because the disease did not yet manifest itself. Depression, sleep apnea, and dysregulation of cytokines are plausible confounders that were not adequately controlled. It may be impossible to be confident that all conceivable confounds are adequately controlled in epidemiological studies of sleep. 

Krueger JM, Obal FJ, Fang J, Kubota T, Taishi P. The role of cytokines in physiological sleep regulation. Ann NY Acad Sci 2001 933 211-221. 

Boyum A, Wiik P, Gustavsson E, Veiby OP, Reseland J, Haugen AH, Opstad PK. The effect of strenuous exercise, caloric deficiency and sleep deprivation on white blood cells, plasma immunoglobulins and cytokines. Scand J Immunol 1996 43 228-235. 

Cytokines are proteins involved in intercellular communication and are produced by many cell types. Cytokines are best known as mediators of the acute-phase response to microbial challenge and to tissue damage. For instance, cytokines are responsible for somnolence and sleep (as well as fever, anorexia, social withdrawal, and other symptoms of the acute-phase response) during infectious diseases. However, cytokines in much smaller concentrations may also have a role in physi-... 

Low doses of IL-ip or TNF-a have little effects on REM sleep but higher doses generally suppress this state of vigilance. Inhibition of REM sleep might be related to fever. However, the febrile response to exogenously administered cytokines can be selectively suppressed without blocking the sleep-promoting activity (82). 

Krueger JM. Cytokines and growth factors in sleep regulation. In Borbely AA, Hayaishi O, Sejnowski TJ, Altman JS, eds. The Regulation of Sleep. Strasbourg HFSP, 2000 122-131. 

Hohagen F, Timmer J, Weyerbrock A, Fritsch-Montero R, Ganter U, Krieger S, Berger M, Bauer J. Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans. Neuropsychobiology 1993 28 9-16. 

Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP (1997) Elevation of plasma cytokines in disorders of excessive daytime sleepiness role of sleep disturbance and obesity. J Clin Endocrinol Metab 82 1313-1316... 

Entzian P, Linnemann K, Schlaak M, Zabel P (1996) Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines. Am J Respir Crit Care Med 153 1080-1086... 

Pro-inflammatory cytokines (see p. 432 et seq.) can also induce sleep, the effect depending on the concentration of the cytokine and the time of day. The effect on the sleep profile (increased non-REM and decreased REM sleep) appears to depend on the increased synthesis of prostaglandin D2 and nitric oxide which then alter the circadian rhythm. It is also known that some pro-inflammatory cytokines can affect the reuptake of 5-HT which plays an important role in regulating the sleep-wake profile. The endogenous fatty acid, oleamide, can cause sedation and induce sleep by activating cannabinoid receptors but also by potentiating the action of benzodiazepines on their receptor sites. Whether such action is of physiological relevance is presently unknown. 

In addition to activation of the HPA axis, the pro-inflammatory cytokines also influence behavior the outcome of this influence is manifested as a synckome known as sickness behavior. This synckome is characterized by a number of behavioral responses including anhedonia (inability to experience pleasure), deareased general activity and exploratory behavior, decreased feeding and sexual activity, and ina eased sleep (Dantzer, 2001, 2004 Lai son and Dunn, 2001). 

An immune analysis during sleep showed an increase of the type-1 monocyte derived cytokines TNF-a and IL-12 and a decrease of the type-2 IL-10 producing monocytes (Dimitrov et al., 2004). In contrary, continuous wakefulness blocked the increase of type-1 and decrease of type-2 cytokines (T. Lange and S. Dimitrov, personal communication). Thus, sleep deprivation may exert therapeutic effects through a low suppression of type-1 cytokines. 

Dimiti ov S, Lairge T, Tiekeir S, Felrm HL, Born J (2004) Sleep associated regulatioir of T helper lAT helper 2 cytokine balairce hr humairs. Brairr Behav Immuir 18 341—348. 

Dimitrov S, Lange T, Tieken S, Fehm HL, Bom J (2004) Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans. Brain Behav Immun 18 341-348. 

In 2004 Okrm and colleagues studied the role of cytokines and growth hormone in the regulation of sleep and narcolepsy. Collectively, proinflammatory cytokines and human growth hormone (HGH), were found to be possibly involved in the development of or the exacerbation of narcolepsy (a disabling neurological sleep disorder characterized by excessive daytime sleepiness and abnormal sleep manifestations). As the role of the immune system in sleep becomes clearer, a better interpretation will be available to assess why narcoleptics have altered cytokine and HGH levels. Future studies should be conducted to fuUy characterize the sources, patterns, and significance of alterations in patterns of proinflammatory cytokines and HGH in narcolepsy. ... 

Endres, S. n-3 Polyunsaturated fatty acids and human cytokines synthesis. Lipids 1997 31 5239-5242. Fadda P, Martellotta MC, Gessa GE, Fratta W. Dopamine and apodes interactions in sleep deprivation. Prog... 

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