0207 Low-Dose Acetylsalicylic Acid Affects Pro-Inflammatory and Pro-Resolving Lipid Mediator Responses to Experimental Sleep Restriction in Healthy Humans

Abstract Introduction Sleep deficiency increases the risk for diseases involving immunopathology, in which inflammation is thought to be an underlying mechanism. A potential way to mitigate health consequences of deficient sleep is to target inflammation. Using low-dose acetylsalicylic acid (ASA, aspirin) as a probe, we have previously shown that low-dose ASA blunts the pro-inflammatory immune response to experimental sleep restriction. The aim of the present study was to investigate whether low-dose ASA affects lipid mediator responses to sleep restriction in healthy humans. Methods We studied 46 healthy adults (19F/27M, 19-63 years) in a randomized crossover trial with 3 protocols each consisting of a 14-day at-home phase followed by an 11-day/10-night in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo) with daily ASA/placebo intake. During in-laboratory stays, sleep opportunity under both sleep restriction conditions was 8h during 2 baseline nights, 4h during 5 nights of restricted sleep, and 8h during 3 nights of recovery sleep. Under the control sleep condition, participants had a sleep opportunity of 8h/night throughout the protocol. Blood samples were analyzed at baseline, after 5 nights of sleep restriction/control sleep, and after 2 nights of recovery sleep/control sleep. Plasma lipids were measured via LC-MS/MS. Data were analyzed using GLMMs. Results Low-dose ASA blunted the pro-inflammatory lipid mediator response to experimental sleep restriction, as manifested in reduced PGE2 and TXB2 levels after sleep restriction and recovery sleep in the sleep restriction/ASA condition compared to sleep restriction/placebo (p<.001). Moreover, low-dose ASA showed complex effects on pro-resolving lipid mediator responses to sleep restriction, including changes in resolvins and maresins (p<.05). Conclusion These findings suggest low-dose ASA may counteract against inflammatory consequences of acute sleep restriction by modulating lipid mediator pathways. This study might pave the way to explore novel pharmacological mechanisms to target specific lipid mediator pathways in order to mitigate immunopathological consequences of sleep deficiency. Support (if any) NIH/NHLBI R01HL136310 to MH; German Research Foundation (DFG) EN1291/1-1 to LCE; NIH/NCRR UL1RR02758 & M01RR01032 to the Harvard Clinical and Translational Science Center; NIH/NCRR S10RR027926, NIH/OD S10OD032292 to the Wayne State University Lipidomics Core Facility.