睡眠和免疫内分泌系统之间的联系是公认的,但是这种关系的性质还没有得到很好的理解。睡眠碎片诱导外周组织和大脑的促炎反应,但它也激活下丘脑-垂体-肾上腺(HPA)轴,释放糖皮质激素(GC)(人类皮质醇和小鼠皮质酮)。尚不清楚糖皮质激素的这种快速释放是否在短期内增强或抑制炎症反应。这项研究的目的是确定阻断或抑制糖皮质激素活性是否会影响急性睡眠碎片(ASF)的炎症反应。雄性C57BL/6J小鼠腹膜内注射0.9%NaCl(载体1),metyrapone(一种糖皮质激素合成抑制剂,溶解在车辆1中),2%乙醇在聚乙二醇(载体2),或者米非司酮(一种糖皮质激素受体拮抗剂,溶解在媒介物2中)在ASF开始前10分钟或无睡眠碎片(NSF)。24小时后,样本是从大脑(前额叶皮层,下丘脑,海马体)和外周(肝脏,脾,脾心,和附睾白色脂肪组织(EWAT))。测量促炎基因表达(TNF-α和IL-1β),然后进行基因表达分析。美替酮治疗影响了ASF期间某些外周组织的促炎细胞因子基因表达,但不是在大脑里.更具体地说,甲吡酮治疗抑制ASF期间EWAT中IL-1β的表达,这意味着GC的促炎作用。然而,在心脏组织中,甲吡酮治疗可增加ASF小鼠的TNF-α表达,提示GC的抗炎作用。米非司酮治疗比甲吡酮产生更显著的结果,在ASF期间减少肝脏(仅NSF小鼠)和心脏组织中的TNF-α表达,表明有促炎作用。相反,在ASF小鼠的脾脏中,米非司酮增加促炎细胞因子(TNF-α和IL-1β),表现出抗炎作用。此外,不管睡眠碎片,米非司酮增加心脏促炎细胞因子基因表达(IL-1β),前额叶皮质(IL-1β),和下丘脑(IL-1β)。结果为皮质酮的促炎和抗炎功能提供了混合证据,以调节急性睡眠不足的炎症反应。
The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces a pro-inflammatory response in peripheral tissues and brain, but it also activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) (cortisol in humans and corticosterone in mice). It is unclear whether this rapid release of glucocorticoids acts to potentiate or dampen the inflammatory response in the short term. The purpose of this study was to determine whether blocking or suppressing glucocorticoid activity will affect the inflammatory response from acute sleep fragmentation (ASF). Male C57BL/6J mice were injected i.p. with either 0.9% NaCl (vehicle 1), metyrapone (a glucocorticoid synthesis inhibitor, dissolved in vehicle 1), 2% ethanol in polyethylene glycol (vehicle 2), or mifepristone (a glucocorticoid receptor antagonist, dissolved in vehicle 2) 10 min before the start of ASF or no sleep fragmentation (NSF). After 24 h, samples were collected from brain (prefrontal cortex, hypothalamus, hippocampus) and periphery (liver, spleen, heart, and epididymal white adipose tissue (EWAT)). Proinflammatory gene expression (TNF-α and IL-1β) was measured, followed by gene expression analysis. Metyrapone treatment affected pro-inflammatory cytokine gene expression during ASF in some peripheral tissues, but not in the brain. More specifically, metyrapone treatment suppressed IL-1β expression in EWAT during ASF, which implies a pro-inflammatory effect of GCs. However, in cardiac tissue, metyrapone treatment increased TNF-α expression in ASF mice, suggesting an anti-inflammatory effect of GCs. Mifepristone treatment yielded more significant results than metyrapone, reducing TNF-α expression in liver (only NSF mice) and cardiac tissue during ASF, indicating a pro-inflammatory role. Conversely, in the spleen of ASF-mice, mifepristone increased pro-inflammatory cytokines (TNF-α and IL-1β), demonstrating an anti-inflammatory role. Furthermore, irrespective of sleep fragmentation, mifepristone increased pro-inflammatory cytokine gene expression in heart (IL-1β), pre-frontal cortex (IL-1β), and hypothalamus (IL-1β). The results provide mixed evidence for pro- and anti-inflammatory functions of corticosterone to regulate inflammatory responses to acute sleep loss.