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Clinical Studies |
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-
(TNF),
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, IL-1ß, and IL-6 are elevated in patients with EDS, we
measured morning plasma levels of TNF, IL-1ß, and IL-6 in 12 sleep
apneics, 11 narcoleptics, 8 idiopathic hypersomniacs, and 10 normal
controls. TNF 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
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 and IL-6 might play a significant role in
mediating sleepiness and fatigue in disorders of EDS in humans.
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T. Yokoe, K. Minoguchi, H. Matsuo, N. Oda, H. Minoguchi, G. Yoshino, T. Hirano, and M. Adachi Elevated Levels of C-Reactive Protein and Interleukin-6 in Patients With Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Continuous Positive Airway Pressure Circulation, March 4, 2003; 107(8): 1129 - 1134. [Abstract] [Full Text] [PDF]
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A. S.M. Shamsuzzaman, M. Winnicki, P. Lanfranchi, R. Wolk, T. Kara, V. Accurso, and V. K. Somers Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea Circulation, May 28, 2002; 105(21): 2462 - 2464. [Abstract] [Full Text] [PDF]
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J.-P. Bastard, M. Maachi, J. T. van Nhieu, C. Jardel, E. Bruckert, A. Grimaldi, J.-J. Robert, J. Capeau, and B. Hainque Adipose Tissue IL-6 Content Correlates with Resistance to Insulin Activation of Glucose Uptake both in Vivo and in Vitro J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2084 - 2089. [Abstract] [Full Text] [PDF]
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I. Lemieux, A. Pascot, D. Prud'homme, N. Almeras, P. Bogaty, A. Nadeau, J. Bergeron, and J.-P. Despres Elevated C-Reactive Protein : Another Component of the Atherothrombotic Profile of Abdominal Obesity Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 961 - 967. [Abstract] [Full Text] [PDF]
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G. Fruhbeck, J. Gomez-Ambrosi, F. J. Muruzabal, and M. A. Burrell The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation Am J Physiol Endocrinol Metab, June 1, 2001; 280(6): E827 - E847. [Abstract] [Full Text] [PDF]
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G. Päth, S. R. Bornstein, M. Gurniak, G. P. Chrousos, W. A. Scherbaum, and H. Hauner Human Breast Adipocytes Express Interleukin-6 (IL-6) and Its Receptor System: Increased IL-6 Production by {beta}-Adrenergic Activation and Effects of IL-6 on Adipocyte Function J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2281 - 2288. [Abstract] [Full Text]
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J.-M. Fernandez-Real, M. Vayreda, C. Richart, C. Gutierrez, M. Broch, J. Vendrell, and W. Ricart Circulating Interleukin 6 Levels, Blood Pressure, and Insulin Sensitivity in Apparently Healthy Men and Women J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1154 - 1159. [Abstract] [Full Text]
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J. M. Bruun, S. B. Pedersen, and B. Richelsen Regulation of Interleukin 8 Production and Gene Expression in Human Adipose Tissue in Vitro J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1267 - 1273. [Abstract] [Full Text]
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A. N. Vgontzas, R. S. Legro, E. O. Bixler, A. Grayev, A. Kales, and G. P. Chrousos Polycystic Ovary Syndrome Is Associated with Obstructive Sleep Apnea and Daytime Sleepiness: Role of Insulin Resistance J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 517 - 520. [Abstract] [Full Text]
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F. Morisson, A. Decary, D. Petit, G. Lavigne, J. Malo, and J. Montplaisir Daytime Sleepiness and EEG Spectral Analysis in Apneic Patients Before and After Treatment With Continuous Positive Airway Pressure Chest, January 1, 2001; 119(1): 45 - 52. [Abstract] [Full Text] [PDF]
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B. L. Wajchenberg Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome Endocr. Rev., December 1, 2000; 21(6): 697 - 738. [Abstract] [Full Text]
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R. SCHULZ, S. MAHMOUDI, K. HATTAR, U. SIBELIUS, H. OLSCHEWSKI, K. MAYER, W. SEEGER, and F. GRIMMINGER Enhanced Release of Superoxide from Polymorphonuclear Neutrophils in Obstructive Sleep Apnea . Impact of Continuous Positive Airway Pressure Therapy Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 566 - 570. [Abstract] [Full Text] [PDF]
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A. N. Vgontzas, E. O. Bixler, D. A. Papanicolaou, G. P. Chrousos, B. R. Bistrian, L. Khaodhiar, M. Visser, and T. B. Harris Chronic Systemic Inflammation in Overweight and Obese Adults JAMA, May 3, 2000; 283(17): 2235 - 2236. [Full Text] [PDF]
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A. N. Vgontzas, D. A. Papanicolaou, E. O. Bixler, K. Hopper, A. Lotsikas, H.-M. Lin, A. Kales, and G. P. Chrousos Sleep Apnea and Daytime Sleepiness and Fatigue: Relation to Visceral Obesity, Insulin Resistance, and Hypercytokinemia J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1151 - 1158. [Abstract] [Full Text]
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D. A. Papanicolaou Interleukin-6: The Endocrine Cytokine J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1331 - 1333. [Full Text]
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R. H. Straub, H. W. Hense, T. Andus, J. Schölmerich, G. A. J. Riegger, and H. Schunkert Hormone Replacement Therapy and Interrelation between Serum Interleukin-6 and Body Mass Index in Postmenopausal Women: A Population-Based Study J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1340 - 1344. [Abstract] [Full Text]
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M. M. Hagan, P. J. Havel, R. J. Seeley, S. C. Woods, N. N. Ekhator, D. G. Baker, K. K. Hill, M. D. Wortman, A. H. Miller, R. L. Gingerich, et al. Cerebrospinal Fluid and Plasma Leptin Measurements: Covariability with Dopamine and Cortisol in Fasting Humans J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3579 - 3585. [Abstract] [Full Text] [PDF]
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A. N. Vgontzas, D. A. Papanicolaou, E. O. Bixler, A. Lotsikas, K. Zachman, A. Kales, P. Prolo, M.-L. Wong, J. Licinio, P. W. Gold, et al. Circadian Interleukin-6 Secretion and Quantity and Depth of Sleep J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2603 - 2607. [Abstract] [Full Text]
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Z. Orban, A. T. Remaley, M. Sampson, Z. Trajanoski, and G. P. Chrousos The Differential Effect of Food Intake and {beta}-Adrenergic Stimulation on Adipose-Derived Hormones and Cytokines in Man J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2126 - 2133. [Abstract] [Full Text]
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N. M. PUNJABI, D. J. O'HEARN, D. N. NEUBAUER, F. J. NIETO, A. R. SCHWARTZ, P. L. SMITH, and K. BANDEEN-ROCHE Modeling Hypersomnolence in Sleep-disordered Breathing . A Novel Approach Using Survival Analysis Am. J. Respir. Crit. Care Med., June 1, 1999; 159(6): 1703 - 1709. [Abstract] [Full Text]
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 G. RITTER Nocturnal desaturation in patients with stable heart failure Heart, December 1, 1998; 80(6): 633b - 634. [Full Text]
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L. S. BENNETT, B. A. LANGFORD, J. R. STRADLING, and R. J. O. DAVIES Sleep Fragmentation Indices as Predictors of Daytime Sleepiness and nCPAP Response in Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., September 1, 1998; 158(3): 778 - 786. [Abstract] [Full Text] [PDF]
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A. N. Vgontzas, E. O. Bixler, T.-L. Tan, D. Kantner, L. F. Martin, and A. Kales Obesity Without Sleep Apnea Is Associated With Daytime Sleepiness Arch Intern Med, June 22, 1998; 158(12): 1333 - 1337. [Abstract] [Full Text] [PDF]
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E. Späth-Schwalbe, K. Hansen, F. Schmidt, H. Schrezenmeier, L. Marshall, K. Burger, H. L. Fehm, and J. Born Acute Effects of Recombinant Human Interleukin-6 on Endocrine and Central Nervous Sleep Functions in Healthy Men J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1573 - 1579. [Abstract] [Full Text]
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S. K. Fried, D. A. Bunkin, and A. S. Greenberg Omental and Subcutaneous Adipose Tissues of Obese Subjects Release Interleukin-6: Depot Difference and Regulation by Glucocorticoid J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 847 - 850. [Abstract] [Full Text]
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M. R. Drange and S. Melmed To Sleep, Perchance To Eat J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1311 - 1312. [Full Text] [PDF]
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