Interleukin-6 levels fluctuate with the light–dark cycle in the brain and peripheral tissues in rats

Guan, Zhonghong; Vgontzas, Alexandros N.; Omori, Takenori; Peng, Xuwen; Bixler, Edward O.; Fang, Jidong

doi:10.1016/j.bbi.2005.01.005

Cited by 40 publications

(25 citation statements)

References 26 publications

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“…These parameters in WKY rats were higher during the rest period (2 HALO) than during the active period (14 HALO) in this study. Similar data were reported in the brain of normotensive rats (35,36). In addition, cardiac IL-1β and IL-6 mRNA levels were shown to increase in SHR (18), which was confirmed in this study.…”

Section: Discussionsupporting

confidence: 79%

Chronopharmacology of Angiotensin II–receptor Blockers in Stroke-Prone Spontaneously Hypertensive Rats

et al. 2011

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Abstract. Protective effect of valsartan (Val), an angiotensin II (AII)-receptor blocker (ARB), against organ damage is reported to depend on the dosing time in hypertensive patients. Dosingtime-dependent effect of Val on survival of stroke-prone spontaneously hypertensive rats (SHRSP) under a 12-h lighting cycle was examined. Val (4 mg/kg per day) and olmesartan medoxomil (OM) (1 mg/kg per day), another ARB with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 HALO (hours after lights on). Dosing-time-dependent differences in plasma drug concentrations and effect on blood pressure (BP) were also evaluated. Survival of SHRSP showed a dosing-time-dependent change during Val therapy, with a peak at 2 HALO and a trough at 14 HALO. OM equally prolonged survival in all groups. The BP-lowering effect persisted for more than 24 h after dosing of Val at 2 HALO and of OM at 2 and 14 HALO, but disappeared at 5.5-h after Val dosing at 14 HALO. Plasma concentrations of Val and OM were higher after dosing at 2 HALO than at 14 HALO. These results suggest that the chronopharmacological phenomenon of Val was partly due to the dosing-time-dependent difference in plasma concentration and subsequent duration of the antihypertensive effect. Slower dissociation of OM from AII receptors might have blunted a potential dosing-time-dependent event.

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Section: Discussionsupporting

confidence: 79%

Chronopharmacology of Angiotensin II–receptor Blockers in Stroke-Prone Spontaneously Hypertensive Rats

et al. 2011

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“…The correlation of sleep to evening-to-morning increases in IL-6 (pg/mL) suggests benefit from sleep, but may also partially reflect circadian rhythm patterns known to associated with variation in IL-6 or itch mediators. 28,29 Some cytokines also serve nonimmune functions such as regulation of central nervous system processes including modulation of mood, sexual behavior, and sleep. Morning IL-6 levels are negatively associated with sleep quality.…”

Section: Discussionmentioning

confidence: 99%

Disease severity, scratching, and sleep quality in patients with atopic dermatitis

Bender¹,

Ballard²,

Canono³

et al. 2008

Journal of the American Academy of Dermatology

158

134

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“…A recent study showed that central administration of rat recombinant IL-6 increases non-REM sleep in these animals [44]. Also, two more recent studies showed that IL-6 in rats [45,46] exhibited a diurnal rhythm with peak values during the light period (which is the sleep period for these animals). This emerging literature from animal studies suggests that IL-6 has a role as a sleep factor and its circadian rhythm is present across species.…”

Section: Il-6 Is a 'Sleep' Cytokine In Animals Alsomentioning

confidence: 99%

IL-6 and Its Circadian Secretion in Humans

Vgontzas¹,

Bixler²,

Lin

et al. 2005

Neuroimmunomodulation

294

192

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Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative ‘sleep factor’ and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of ‘detrended’ data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.

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Interleukin-6 levels fluctuate with the light–dark cycle in the brain and peripheral tissues in rats

Cited by 40 publications

References 26 publications

Chronopharmacology of Angiotensin II–receptor Blockers in Stroke-Prone Spontaneously Hypertensive Rats

Chronopharmacology of Angiotensin II–receptor Blockers in Stroke-Prone Spontaneously Hypertensive Rats

Disease severity, scratching, and sleep quality in patients with atopic dermatitis

IL-6 and Its Circadian Secretion in Humans

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