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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 5 1313-1316
Copyright © 1997 by The Endocrine Society

Clinical Studies

Elevation of Plasma Cytokines in Disorders of Excessive Daytime Sleepiness: Role of Sleep Disturbance and Obesity

Alexandros N. Vgontzas, Dimitris A. Papanicolaou, Edward O. Bixler, Anthony Kales, Kathy Tyson and George P. Chrousos

Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University (A.N.V., E.O.B., A.K., K.T.), Hershey, Pennsylvania 17033; the Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health (D.A.P., G.P.C.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Alexandros N. Vgontzas, M.D., Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University, 500 University Drive, Hershey, Pennsylvania 17033.

Excessive daytime sleepiness (EDS) and fatigue are frequent symptoms in the general population and the chief complaint of the majority of patients at Sleep Disorders Centers. There is evidence that the inflammatory cytokines tumor necrosis factor-{alpha} (TNF{alpha}), interleukin-1ß (IL-1ß), and IL-6 are involved in physiological sleep regulation and that their administration to humans is associated with sleepiness and fatigue. To explore whether plasma levels of TNF{alpha}, IL-1ß, and IL-6 are elevated in patients with EDS, we measured morning plasma levels of TNF{alpha}, IL-1ß, 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 compared to that in normal controls (P < 0.001 and P = 0.001, respectively). Plasma IL-1ß concentrations were not different between sleep disorder patients and controls, whereas IL-6 was markedly and significantly elevated in sleep apneics compared to that in normal controls (P = 0.028). The primary factor influencing TNF{alpha} values was the degree of nocturnal sleep disturbance, whereas the primary determinant for IL-6 levels was the body mass index. Our findings suggest that TNF{alpha} and IL-6 might play a significant role in mediating sleepiness and fatigue in disorders of EDS in humans.




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