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.

The proinflammatory cytokines, TNFalpha and IL-6, are elevated in obstructive sleep apnea (OSA) and have been proposed as mediators of excessive daytime sleepiness in humans. We tested the effects of etanercept, a medication that neutralizes TNFalpha and is approved by the FDA for the treatment of rheumatoid arthritis, in eight obese male apneics. These patients participated in a pilot, placebo-controlled, double-blind study during which nighttime polysomnography, multiple sleep latency test, and fasting blood glucose and plasma levels of IL-6, C-reactive protein, insulin, and adiponectin were obtained. There was a significant and marked decrease in sleepiness by etanercept, which increased sleep latency during the multiple sleep latency test by 3.1 +/- 1.0 min (P < 0.05) compared with placebo. Also, the number of apneas/hypopneas per hour was reduced significantly by the drug compared with placebo (52.8 +/- 9.1 vs. 44.3 +/- 10.3; adjusted difference, -8.4 +/- 2.3; P < 0.05). Furthermore, IL-6 levels were significantly decreased after etanercept administration compared with placebo (3.8 +/- 0.9 vs. 1.9 +/- 0.4 pg/ml; adjusted difference, -1.9 +/- 0.5; P < 0.01). However, no differences were observed in etanercept vs. placebo in the levels of fasting blood glucose and plasma C-reactive protein, insulin, and adiponectin. We conclude that neutralizing TNFalpha activity is associated with a significant reduction of objective sleepiness in obese patients with OSA. This effect, which is about 3-fold higher than the reported effects of continuous positive airway pressure on objective sleepiness in patients with OSA (0.9 vs. 3.1 min), suggests that proinflammatory cytokines contribute to the pathogenesis of OSA/sleepiness.

No abstract

The aim of this study was to determine if the lockdown measures applied due to the pandemic of Coronavirus Disease 2019 (COVID-19) affected the sleep of the general population and health professionals in six different countries (Greece, Switzerland, Austria, Germany, France, and Brazil). We used a web-based survey with a short questionnaire of 13 questions, translated into four languages (Greek, German, French, and Portuguese). The questionnaire included information about demographic and professional data, quantitative and qualitative characteristics of sleep, degree of abidance in lockdown measures, and data about illness or close contact with active confirmed cases of COVID-19. Initially, 2093 individuals participated. After exclusion of those who did not report their duration of sleep, the final sample comprised 1908 participants (Greek, n = 1271; German, n = 257, French, n = 48; Portuguese, n = 332), aged 42.6 ± 12.7 years, who were considered for further analysis. A main effect of the lockdown week on sleep duration was observed (+0.25 h; 95% confidence intervals, CI, 0.17, 0.32; p < 0.001), with the total sleep time of the lockdown week being longer than that under normal conditions. A week*occupation interaction on sleep duration was demonstrated (p < 0.001, η2 = 0.012). Sleep duration remained stable in health professionals (−0.18 h; 95% CI −0.36, 0.01; p = 0.063), whereas it increased in other occupations by 0.31 h (95% CI, 0.24, 0.39; p < 0.001). In terms of sleep quality, 15% of participants characterized their sleep as bad and 37.9% as average during the lockdown week. Almost 1 in 3 individuals (31.3%) reported worse quality of sleep during the lockdown week than under normal conditions. Sleep during the lockdown week was characterized as good by 47.1%, but only 38% of the health professionals group. In conclusion, the COVID−19 pandemic and lockdown affected sleep in different ways, depending on age, level of education, occupation, and country of residence.