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Does acute sleep deficiency affect markers of inflammatory resolution? Monika Haack, Vrushank Bhatt, Moussa, Diolombi, Janet Mullington Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA Introduction Various pro-inflammatory markers (e.g., IL-6, TNF, prostaglandins) robustly respond to acute sleep deficiency, whether measured in urine, plasma, or immune cells. It has been repeatedly shown that these markers do not return to baseline after one or two nights of recovery sleep, suggesting that acute sleep deficiency may disrupt the process of inflammatory resolution. This poster introduces markers involved in resolution physiology, which has been mainly studied in pre-clinical animal models, but may give promise to human translation. How does inflammation resolve? The resolution of inflammation is an active, rather than passive process. The newly discovered lipid mediators resolvins, maresins, lipoxins, and protectins (Serhan et al., 2015) are part of this active biochemical program enabling the resolution of inflammation and the return to baseline (Figure 1). These lipid mediators derive from polyunsaturated fatty acids (PUFA), such as the omega-3 PUFAs EPA and DHA, and can stimulate key cellular events (counter-regulation of chemokines/cytokines, cessation of neutrophil tissue infiltration, stimulation of macrophage-mediated actions etc.). Preliminary data Since proresolving markers have never been measured in the context of sleep, we first investigated whether they are detectable in human plasma of healthy young participants, and whether they respond to acute sleep deficiency followed by recovery sleep. Results: Methods: Measurement of inflammatory and proresolving markers in blood obtained from an experimental model resembling common sleep-wake behaviors of restricting sleep during week/work days and catching up on sleep during weekend/ work-off days. Figure 2: IL-6 positive Measures: monocytes increase upon - IL-6 positive monocytes repeated exposure to sleep after stimulation with LPS, restriction, without returning to baseline levels after quantified with flow cytointermittent recovery sleep metry. (N=14). The pro-resolving - Proresolving markers delipid mediator resolvin E3 termined in plasma, using decreases after 5 nights of liquid chromatography-tanrestricted sleep, and further dem mass spectrometry decreases upon 2 nights of (LC-MS-MS; Lipid Mediator recovery sleep, suggesting Metabololipidomics Core, that sleep deficiency interferes with the active Brigham and Women’s process of inflammatory Hospital Boston, Director resolution (N=2). Prof. Serhan). Conclusion Figure 1: Lipid-mediator biosynthesis in the resolution of acute inflammation that enables the return to baseline. Adapted from Serhan et al., 2015. - First results from this work-in-progress suggest that acute sleep deficiency not only affects proinflammatory markers, but also markers contributing to the active process of inflammatory resolution. The balance between proinflammatory and proresovling markers may be an area ripe for exploring as an inflammatory-related biomarker of acute and chronic sleep deficiency. References. Support. Serhan CN, Chiang N, Dalli J, Levy BD. Lipid Mediators in the Resolution of Inflammation. Cold Spring Harbor Perspectives in Biology 2015;7. NHLBI R01 HL105544 to MH; National Center of Research Resources UL1 TR001102 to the Harvard Clinical and Translational Science Center. [email protected]