Patterns of Sleep Restriction and Recovery: The Inflammatory Resolution Pathways

睡眠限制和恢复的模式：炎症消退途径

• 批准号: 10368989
• 负责人: MONIKA HAACK
• 金额: $ 76.56万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368989
• 关键词: Affect; Age; Aspirin; Back; Behavior; Biological Markers; Blood specimen; Data; Development; Dose; Down-Regulation; Experimental Models; Exposure to; Failure; Future; Goals; Homeostasis; Hospitals; Human; Individual; Inflammation; Inflammatory; Inflammatory Response; Interleukin-6; Interleukins; Laboratories; Lead; Length of Stay; Liquid Chromatography; Measures; Mediator of activation protein; Non-Steroidal Anti-Inflammatory Agents; Nonesterified Fatty Acids; Omega-3 Fatty Acids; Participant; Pathogenesis; Pathway interactions; Pattern; Pharmacology; Phase; Placebos; Play; Polysomnography; Process; Production; Recovery; Recurrence; Reporting; Resolution; Role; Series; Signal Transduction; Sleep; Sleep Deprivation; Sleep disturbances; Testing; Time; Up-Regulation; Woman; Work; base; chemokine; cytokine; design; disorder risk; experience; hospital utilization; human disease; inflammatory marker; lipid biosynthesis; lipid mediator; men; monocyte; novel; novel strategies; response; shift work; sleep behavior; sleep health; sleep pattern; sleep regulation; tandem mass spectrometry

PROJECT SUMMARY Low-grade or unresolved inflammation is involved in the pathogenesis of many human diseases. Common sleep patterns of restricting sleep during the work week and ‘catching up’ on sleep over the weekend lead to inflammatory upregulation that does not recover completely after the weekend. Goal of this proposal is to investigate, for the first time, inflammatory resolution pathways. Inflammatory resolution mediators, such as resolvins, are derived from omega-3 free fatty acids and actively ‘turn-off’ inflammation. Based on preliminary data from our lab, we hypothesize that common sleep restriction- recovery patterns disrupt inflammatory resolution pathways, making it difficult to return to inflammatory homeostasis. If true, pharmacologically increasing the body’s natural production of endogenous inflammatory resolution mediators may one day provide a way to reduce the detrimental inflammatory consequences of common sleep restriction-recovery patterns. The hypothesis will be tested using an experimental model that mimics common patterns of restricting sleep on week days and ‘catching up’ on sleep on the weekend. The proposal will further utilize the unique ability of low-dose aspirin, which – like no other non-steroidal anti-inflammatory drug – is able to activate inflammatory resolution pathways. Healthy women and men between the ages of 18 to 50 years will be tested under three 10-day long in-hospital stays, during which they will be exposed to control sleep or common patterns of sleep restriction-recovery. The two sleep restriction-recovery stays will be combined with preemptive administration of low-dose aspirin or placebo. Aim 1 will investigate whether exposure to commonly experienced sleep patterns of sleep restriction followed by recovery sleep will not only activate inflammatory (e.g., interleukin-6), but disrupt inflammatory resolution pathways (e.g., resolvins), as well. Aim 2 will test that activation of inflammatory resolution pathways by aspirin dampens the inflammatory response to sleep restriction. Aim 3 is target-unspecific and will profile a wide range of resolution lipid mediators using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) platform, which may fuel the search of a biomarker to be used in the monitoring of sleep health. Targeting inflammatory resolution pathways could provide a novel, non-behavioral strategy to mitigate both inflammatory consequences and future disease risks in those undergoing periods of sleep restriction-recovery patterns – a behavior pattern that is unlikely to be eradicated in the near future, as changes in sleep are generally difficult to make and to maintain.

项目摘要 低度或未解决的炎症参与许多人类疾病的发病机制。共同 在工作周限制睡眠和在周末“补觉”的睡眠模式导致 炎症上调，周末后不完全恢复。 该提案的目的是首次调查炎症消退途径。炎性 消退介质，如消退素，来源于ω-3游离脂肪酸，并主动“关闭” 炎症基于我们实验室的初步数据，我们假设常见的睡眠限制- 恢复模式会破坏炎症消退途径，使其难以恢复 炎性稳态如果这是真的， 内源性炎症介质可能有一天会提供一种方法，以减少有害的 常见的睡眠限制-恢复模式的炎症后果。 该假设将使用一个模拟常见限制模式的实验模型进行测试。 工作日睡觉，周末补觉。该提案将进一步利用 低剂量阿司匹林的能力，它-像没有其他非甾体抗炎药-能够激活 炎症消退途径。年龄在18至50岁之间的健康女性和男性将接受测试 少于三个10天的住院时间，在此期间，他们将接触到控制睡眠或常见的 睡眠限制-恢复模式。两次睡眠限制-恢复停留将与 预先给予低剂量阿司匹林或安慰剂。目标1将调查是否暴露于 通常经历的睡眠限制后恢复睡眠的睡眠模式不仅会激活 炎症（例如，白细胞介素-6），但破坏炎症消退途径（例如，Resolvins），也是。目的2 将测试阿司匹林对炎症消退途径的激活是否抑制了炎症反应， 睡眠限制Aim 3是非靶点特异性的，将使用 液相色谱/串联质谱（LC-MS/MS）平台，这可能会推动搜索 这是一种用于监测睡眠健康的生物标志物。 针对炎症消退途径可以提供一种新的非行为策略来缓解这两种情况。 睡眠限制-恢复期患者的炎症后果和未来疾病风险 模式-一种行为模式，不太可能在不久的将来被根除，因为睡眠的变化是 通常难以制造和维护。