THE ROLE OF CYTOKINES IN SLEEPINESS AND SLEEP APNEA

Project: Research project

Project Details

Description

DESCRIPTION (applicant's abstract): Excessive daytime sleepiness (EDS) is a
major public health concern, in part because individuals suffering from EDS
often are not productive at work, are more susceptible to accidents, and
generally are unable to function normally during the day. EDS is one of the
major manifestations of individuals suffering from obstructive sleep apnea
(OSA) and is frequently reported by obese individuals without sleep apnea. The
mechanisms underlying EDS observed in both types of these individuals are not
clear. We have recently demonstrated that the pro-inflammatory and
fatigue-inducing cytokines, tumor necrosis factor-alpha (TNFalpha) and
interleukin-6 (IL-6), assayed in single plasma samples, are elevated in
subjects with disorders of EDS. In addition, in preliminary studies, we
demonstrated that these two cytokines are elevated in obese, compared to lean
subjects, and that both sleep disturbance and obesity contribute to the
cytokine elevation. More recently, we showed that daytime plasma levels of IL-6
are elevated in experimentally-induced EDS by the use of sleep deprivation and
that a good night's sleep is associated with decreased daytime levels in
healthy young subjects. There is a large literature implicating several
pro-inflammatory cytokines in the regulation of sleep in animals; however,
cytokine research on sleep in humans has been very limited. The fundamental
hypothesis to be tested by the proposed studies is that the pro-inflammatory
cytokines, TNFalpha and IL-6, are associated with and may contribute to EDS. We
will test this hypothesis by determining the circadian secretory patterns of
TNFalpha and IL-6 in plasma obtained from subjects that exhibit EDS associated
with OSA or obesity. Also, we will determine whether nighttime nasal CPAP
reduces daytime plasma TNFalpha and IL-6 concentrations in sleep apneics. In
addition, we will experimentally induce EDS in healthy young subjects by the
use of total sleep deprivation or one week of sleep restriction, which mimics
real life-situations, to determine the relationship between the pattern of
daytime plasma TNFalpha and IL-6 concentrations and daytime sleepiness as
measured objectively using MSLT. Finally, we will assess the effects of daytime
napping, in healthy subjects, on post-nap sleepiness and TNFalpha and IL-6
secretion. In these studies, we will use a series of experimental techniques
including nighttime polysomnography, MSLT, computerized EEG, actigraphy,
24-hour blood sampling, 24-hour recording of core body temperature, and assays
for TNFalpha and IL-6. These studies collectively will provide additional
evidence for a role of TNFalpha and IL-6 in EDS and lay the foundation for the
development of potential therapeutic interventions.
StatusFinished
Effective start/end date8/1/006/30/11

Funding

  • National Heart, Lung, and Blood Institute: $250,351.00
  • National Heart, Lung, and Blood Institute: $234,900.00
  • National Heart, Lung, and Blood Institute: $243,090.00
  • National Heart, Lung, and Blood Institute: $234,900.00
  • National Heart, Lung, and Blood Institute: $234,900.00
  • National Heart, Lung, and Blood Institute: $256,375.00
  • National Heart, Lung, and Blood Institute: $243,090.00
  • National Heart, Lung, and Blood Institute: $243,090.00
  • National Heart, Lung, and Blood Institute: $234,900.00

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