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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 [lt ] .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 [lt ] .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 [lt ] .05). Also, while TNF secretion in controls showed a distinct circadian rhythm
with a peak close and prior to the offset of sleep (P [lt ] .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 [lt ] .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.
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© 2002 Published by Elsevier Inc. All rights reserved.
