1. 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  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.  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. INTRODUCTION STUDY DESIGN Figure 1: IL-6 levels DISCUSSION FUTURE DIRECTIONS Program # 615.7 METHODS 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. 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 IL-6 Measurement: Plasma concentrations of IL-6 were measured using high sensitivity immunosorbent assay (R&D Systems ELISA), CV<15%. 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. Figure 2:  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.  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.  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 pro- inflammatory cytokine and potentially detrimental actions of IL-6.  IL-6 levels return to baseline levels after recovery sleep. ACKNOWLEDGEMENT REFERENCES This work was supported by science research funds from National Institute of Health (HL-106782) and Harvard Catalyst CTSC NIH UL1 TR001102.  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.  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. RESULTS VariableControlSleep Restriction Women/Men11/1111/10 Age, years31+2 BMI, kg/m 2 24+1 Habitual Sleep, h7.8+0.1 Sleep Period Sleep period with intensive physiological monitoring Blood Draw Urine collection (morning) Urine collection (night) 24 hr periods with PSG 1 2 3 4 5