title: Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime.
abstract: Chronic insomnia, by far the most commonly encountered sleep disorder in medical practice, is characterized by difficulty falling or staying asleep at night and increased fatigue during the day. Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are fatigue-inducing cytokines, and the daytime secretion of IL-6 is negatively influenced by the quantity and quality of the previous night's sleep. We hypothesize that the poor quality of insomniacs' sleep is associated with a hypersecretion of these 2 cytokines during the daytime, which, in turn, correlates with the fatigue experienced by these patients. Eleven young insomniacs (6 men and 5 women) and 11 (8 men and 3 women) age- and body mass index (BMI)-matched healthy controls participated in the study. Subjects were recorded in the sleep laboratory for 4 consecutive nights and serial 24-hour plasma measures of IL-6 and TNF were obtained during the 4th day. Insomniacs compared to controls slept poorly (sleep latency and wake were increased, whereas percentage sleep time was decreased during baseline nights, all P <.05). The mean 24-hour IL-6 and TNF secretions were not different between insomniacs and controls. However, the difference in the change (increase) of IL-6 plasma levels from midafternoon (2 PM) to evening (9 PM) between insomniacs and controls was significant (P <.01). Furthermore, cosinor analysis showed a significant shift of the major peak of IL-6 secretion from nighttime (4 AM) to evening (7 PM) in insomniacs compared to controls (P <.05). Also, while TNF secretion in controls showed a distinct circadian rhythm with a peak close and prior to the offset of sleep (P <.05), such a rhythm was not present in insomniacs. Finally, daytime secretion of TNF in insomniacs was characterized by a regular rhythm of 4 hours (P <.05); such a distinct periodicity was not present in controls. We conclude that chronic insomnia is associated with a shift of IL-6 and TNF secretion from nighttime to daytime, which may explain the daytime fatigue and performance decrements associated with this disorder. The daytime shift of IL-6 and TNF secretion, combined with a 24-hour hypersecretion of cortisol, an arousal hormone, may explain the insomniacs' daytime fatigue and difficulty falling asleep.
authors.affiliation: Sleep Research and Treatment Center, Department of Psychiatry, and Health Evaluation Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Vgontzas
authors.forename: M
authors.initials: M
authors.lastname: Zoumakis
authors.forename: D A
authors.initials: DA
authors.lastname: Papanicolaou
authors.forename: E O
authors.initials: EO
authors.lastname: Bixler
authors.forename: P
authors.initials: P
authors.lastname: Prolo
authors.forename: H-M
authors.initials: HM
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Vela-Bueno
authors.forename: A
authors.initials: A
authors.lastname: Kales
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002908:Chronic Disease; D002940:Circadian Rhythm; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D008297:Male; D010507:Periodicity; D007319:Sleep Initiation and Maintenance Disorders / Q000503:physiopathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone