0174 Using Low-Dose Acetylsalicylic Acid to Target Inflammation in Response to Experimental Sleep Restriction in Humans

Abstract Introduction Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple chronic diseases. Inflammation is considered a mechanism through which deficient sleep acts as risk factor for these diseases. Thus, mitigating inflammation might be a potential way to diminish negative health consequences related to sleep deficiency. To investigate a pharmacological approach for this, we used low-dose acetylsalicylic acid (ASA, aspirin), known for its counter-inflammatory actions including the cyclooxygenase (COX)-, NF-kB-, and resolution-pathways. Our aim was to investigate whether low-dose ASA can blunt the pro-inflammatory response to experimental sleep restriction. Methods 46 healthy adults (19F/27M, 19-63 years) participated in a randomized placebo-controlled crossover trial with 3 protocols each consisting of a 14-day at-home phase followed by an 11-day (10-night) in-hospital stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) during the at-home phase and in-hospital stay. Each in-hospital stay started with 2 nights of 8h-sleep opportunity. Then, under the sleep restriction conditions, participants were exposed to 5 nights of 4h-sleep opportunity, followed by 3 nights of recovery sleep (8h/night). The control sleep condition provided 8h-sleep opportunity throughout the in-hospital stay. Sleep and immunologic/hematologic measures were assessed at baseline, after the 5th night of sleep restriction/control sleep, and after the 2nd night of recovery sleep. Generalized linear mixed models were used for analysis. Results Administration of low-dose ASA reduced interleukin (IL)-6 expression (p<.05 for condition*day) and COX-1/COX-2 double positive cells in lipopolysaccharide (LPS)-stimulated monocytes (p<.05 for condition) as well as C-reactive protein (CRP) serum levels (p<.01 for condition) in the sleep restriction condition compared to placebo. Baseline comparisons revealed no differences between conditions (p>.05 for condition). Conclusion The results show that preemptive administration of low-dose ASA can reduce pro-inflammatory responses to experimental sleep restriction in humans. These findings may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing periods of sleep deficiency. Support (if any) NIH/NHLBI R01-HL136310; NIH/NCRR UL1-RR02758, M01-RR01032; German Research Foundation (DFG) EN1291/1-1; SRSF Career Development Award.