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EFFECT OF REPEATED EXPOSURE TO SLEEP RESTRICTION ON INTERLEUKIN 6 LEVELS IN HUMANS Vrushank Dharmesh Bhatt, Moussa Diolombi, Monika Haack, Janet Mullington Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215 INTRODUCTION Program # 615.7 STUDY DESIGN Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Sleep Period Sleep period with intensive physiological monitoring Blood Draw Urine collection (morning) Urine collection (night) 24 hr periods with PSG Previous studies have suggested that IL-6 is a putative ‘sleep factor’ and its circadian secretion correlates with sleep/sleepiness. Short periods of experimental sleep restriction have been shown to elevate IL-6, which has been suggested to increase the risk for cardiometabolic diseases. However, the effect of repeated exposure to sleep restriction on IL-6 is unknown. METHODS RESULTS Study Design: Participants were randomized to a 22-day study of repeated cycles of sleep restriction (4hr sleep/night for 3 nights followed by one recovery sleep, 4 cycles) or routine sleep (8hr sleep/night), following two nights of baseline sleep. DISCUSSION Night-time Blood Draw at 2245 The sleep restriction group showed a significant increase in IL-6 levels in the morning during the first sleep restriction cycle, exceeding control levels by 20% (p<0.05). These levels did not return to baseline in the remaining sleep restriction cycles when compared with the control group. 1.8 SR1 SR2 SR4 SR3 1.6 IL-6 Measurement: Plasma concentrations of IL-6 were measured using high sensitivity immunosorbent assay (R&D Systems ELISA), CV<15%. 1.4 IL-6 (pg/ml) Blood Sampling: Blood was sampled from fasting recumbent participants in the morning after awakening, during baseline, third day of each sleep restriction or control cycle, and following recovery. Total- 13 blood draws Condition 4 Condition 8 1.2 1 These data suggest that a good night's sleep is associated with decreased daytime secretion of IL-6 and a decreased exposure of tissues to this proinflammatory cytokine and potentially detrimental actions of IL-6. 0.8 Study Environment: Participants remained in the Clinical Research Center for the duration of study, with controlled fluid and calorie intake, with normal interaction and physical activity. Variable Control Sleep Restriction Women/Men 11/11 11/10 Age, years 31+2 0.6 3 6 24+1 10 14 18 20 Day IL-6 levels return to baseline levels after recovery sleep. Figure 1: IL-6 levels Morning-time Blood Draw at 0715 1.6 31+2 SR1 SR3 SR2 24+1 FUTURE DIRECTIONS SR4 * * 1.5 BMI, kg/m2 According to recent findings, IL-6 levels are associated with increased mortality in elderly. So the possibility that anti-inflammatory therapies might provide a new approach to cardiovascular disease treatment and prevention. 1.4 Habitual Sleep, h 7.8+0.1 7.8+0.1 1.3 • 1 IL-6 (pg/ml) 1.2 REFERENCES Though there was a slight increase in the IL-6 levels in the sleep restriction group in the night after the first sleep restriction cycle, this increase was not significant as compared to the baseline levels. Condition 4 Condition 8 1.1 1 0.9 • 2 0.8 • 3 Other inflammation markers will be analyzed to elucidate the exact mechanism for understanding the potential association of these cytokines with sleep, health and well-being. 0.7 • 4 ACKNOWLEDGEMENT 0.6 4 • 5 7 11 15 Day Figure 2: 19 22 This work was supported by science research funds from National Institute of Health (HL-106782) and Harvard Catalyst CTSC NIH UL1 TR001102.