ELEVATION OF PLASMA CYTOKINES IN DISORDERS OF EXCESSIVE DAYTIME SLEEPINESS - ROLE OF SLEEP DISTURBANCE AND OBESITY

Excessive daytime sleepiness (EDS) and fatigue are frequent symptoms i n the general population and the chief complaint of the majority of pa tients at Sleep Disorders Centers. There is evidence that the inflamma tory cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6 are involved in physiological sleep regulat ion and that their administration to humans is associated with sleepin ess and fatigue. To explore whether plasma levels of TNF alpha, IL-1 b eta, and IL-6 are elevated in patients with EDS, we measured morning p lasma levels of TNF alpha, IL-1 beta, and IL-6 in 12 sleep apneics, 11 narcoleptics, 8 idiopathic hypersomniacs, and 10 normal controls. TNF alpha was significantly elevated in sleep apneics and narcoleptics co mpared to that in normal controls (P = 0.001 and P = 0.001, respective ly). Plasma IL-1 beta concentrations were not different between sleep disorder patients and controls, whereas IL-6 was markedly and signific antly elevated in sleep apneics compared to that in normal controls (P = 0.028). The primary factor influencing TNF alpha values was the deg ree of nocturnal sleep disturbance, whereas the primary determinant fo r IL-6 levels was the body mass index. Our findings suggest that TNF a lpha and IL-6 might play a significant role in mediating sleepiness an d fatigue in disorders of EDS in humans.