Consequences of chronic exposure to cytokines of the innate immune system on sleep
in humans and the association of cytokine-induced sleep alterations with behavior,
motor performance, and cortisol secretion are unknown.
Thirty-one patients with hepatitis C without pre-existing sleep disorders underwent
nighttime polysomnography, daytime multiple sleep latency testing, behavioral assessments,
neuropsychological testing, and serial blood sampling at baseline and after ∼12 weeks
of either treatment with the innate immune cytokine interferon (IFN)-alpha (n = 19)
or no treatment (n = 12). Fatigue and sleepiness were assessed using the Multidimensional
Fatigue Inventory and Epworth Sleepiness Scale.
Interferon-alpha administration led to significant increases in wake after sleep onset
and significant decreases in stage 3/4 sleep and sleep efficiency. Rapid eye movement
latency and stage 2 sleep were significantly increased during IFN-alpha treatment.
Decreases in stage 3/4 sleep and increases in rapid eye movement latency were associated
with increases in fatigue, whereas decreases in sleep efficiency were associated with
reduced motor speed. Increased wake after sleep onset was associated with increased
evening plasma cortisol. Despite IFN-alpha-induced increases in fatigue, daytime sleepiness
did not increase. In fact, IFN-alpha-treated patients exhibited decreased propensity
to fall asleep during daytime nap opportunities.
Chronic exposure to an innate immune cytokine reduced sleep continuity and depth and
induced a sleep pattern consistent with insomnia and hyperarousal. These data suggest
that innate immune cytokines may provide a mechanistic link between disorders associated
with chronic inflammation, including medical and/or psychiatric illnesses and insomnia,
which, in turn, is associated with fatigue, motor slowing, and altered cortisol.
Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All