Circadian Interleukin-6 Secretion and Quantity and Depth of Sleep

Abstract

Patients with pathologically increased daytime sleepiness and fatigue have elevated levels of circulating interleukin-6 (IL-6). The latter is an inflammatory cytokine, which causes sickness manifestations, including somnolence and fatigue, and activation of the hypothalamic-pituitary-adrenal axis. In this study, we examined: 1) the relation between serial measurements of plasma IL-6 and quantity and depth of sleep, evaluated by polysomnography; and 2) the effects of sleep deprivation on the nyctohemeral pattern of IL-6 secretion. Eight healthy young male volunteers were sampled for 24 h twice, at the baseline state, after a normal night's sleep and after total overnight sleep deprivation. At the baseline state, IL-6 was secreted in a biphasic circadian pattern with two nadirs at 0800 and 2100 and two zeniths at 1900 and 0500 (P < 0.01). The baseline amount of sleep correlated negatively with the overall daytime secretion of the cytokine (P < 0.05). Also, depth of sleep at baseline correlated negatively with the postdeprivation increase of daytime secretion of IL-6 (P < 0.05). Sleep deprivation changed the temporal pattern of circadian IL-6 secretion but not the overall amount. Indeed, during the post-deprivation period, the mean daytime (0800-2200 h) levels of IL-6 were significantly higher (P < 0.05), whereas the nighttime (2200-0600 h) levels were lower than the predeprivation values. Thus, sleep-deprived subjects had daytime oversecretion and nighttime under-secretion of IL-6; the former might be responsible for their daylong somnolence and fatigue, the latter for the better quality (depth) of their sleep. These data suggest that a good night's sleep is associated with decreased daytime secretion of IL-6 and a good sense of well-being and that good sleep is associated with decreased exposure of tissues to the proinflammatory and potentially detrimental actions of IL-6. Sleep deprivation increases daytime IL-6 and causes somnolence and fatigue during the next day, whereas postdeprivation decreases nighttime IL-6 and is associated with deeper sleep.

Chronic stress and age-related increases in the proinflammatory cytokine IL-6

“…Other researchers have demonstrated that higher plasma IL-6 levels are associated with adverse health habits: values are higher in smokers than nonsmokers, in individuals who report less physical activity, in those whose sleep is impaired, and in those with a higher BMI, all behaviors that are adversely affected by stress (14,34,37,(50)(51)(52). Although the linkage between caregiving and IL-6 was still significant in our data after accounting for these health behaviors, chronic stressors are also likely to affect IL-6 and thus health through these pathways as well.…”

Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea

“…Increased daytime plasma levels of IL-6 were also noted after sleep deprivation and in patients with excessive daytime sleepiness. 4,14,20 IL-6 is one of the key regulators of CRP synthesis by the liver. 5 The repetitive apneas during OSA induce not only hypoxemia, but also sleep fragmentation with consequent insufficient sleep and daytime somnolence.…”

“…Sleep deprivation also induces an increase in cytokines. 4,14 We tested the hypothesis that OSA patients have increased plasma CRP. …”

Neuroimmunology of Disordered Sleep in Depression and Alcoholism

“…However, in humans, acute peripheral administration of IL-6 reduces delta sleep in the first half of the night when circulating levels of IL-6 are elevated (Späth-Schwalbe et al 1998). Vgontzas and colleagues have further found that daytime elevations of circulating IL-6 are associated with severity of sleepiness and fatigue in sleep disordered patients (Vgontzas et al 1997), and that sleep deprivation leads to daytime over-secretion of IL-6 (Vgontzas et al 1999) in which daytime plasma levels of IL-6 negatively correlate with amounts of slow wave sleep. In view of this converging evidence, it is tempting to speculate about a link between cytokines and disordered sleep in the African-American alcoholics in which cytokine abnormalities contribute the severity of sleep disturbance in these patients.…”