Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076 Tübingen, Germany.
Department of Neuroendocrinology, University of Lübeck, 23538 Lübeck, Germany.
Brain Behav Immun. 2015 Jul;47:178-85. doi: 10.1016/j.bbi.2014.11.012. Epub 2014 Dec 20.
Pro-inflammatory cytokines like interleukin-1 beta (IL-1) are major players in the interaction between the immune system and the central nervous system. Various animal studies report a sleep-promoting effect of IL-1 leading to enhanced slow wave sleep (SWS). Moreover, this cytokine was shown to affect hippocampus-dependent memory. However, the role of IL-1 in human sleep and memory is not yet understood. We administered the synthetic IL-1 receptor antagonist anakinra (IL-1ra) in healthy humans (100mg, subcutaneously, before sleep; n=16) to investigate the role of IL-1 signaling in sleep regulation and sleep-dependent declarative memory consolidation. Inasmuch monocytes have been considered a model for central nervous microglia, we monitored cytokine production in classical and non-classical blood monocytes to gain clues about how central nervous effects of IL-1ra are conveyed. Contrary to our expectation, IL-1ra increased EEG slow wave activity during SWS and non-rapid eye movement (NonREM) sleep, indicating a deepening of sleep, while sleep-associated memory consolidation remained unchanged. Moreover, IL-1ra slightly increased prolactin and reduced cortisol levels during sleep. Production of IL-1 by classical monocytes was diminished after IL-1ra. The discrepancy to findings in animal studies might reflect species differences and underlines the importance of studying cytokine effects in humans.
促炎细胞因子，如白细胞介素-1β（IL-1），是免疫系统和中枢神经系统相互作用的主要参与者。各种动物研究报告称，IL-1 具有促进睡眠的作用，导致慢波睡眠（SWS）增加。此外，这种细胞因子被证明会影响海马体依赖的记忆。然而，IL-1 在人类睡眠和记忆中的作用尚不清楚。我们在健康人类（16 人）中给予合成的 IL-1 受体拮抗剂 anakinra（IL-1ra），以研究 IL-1 信号在睡眠调节和睡眠依赖性陈述性记忆巩固中的作用。由于单核细胞被认为是中枢神经系统小胶质细胞的模型，我们监测了经典和非经典血液单核细胞中的细胞因子产生，以了解 IL-1ra 的中枢神经系统效应是如何传递的。与我们的预期相反，IL-1ra 在 SWS 和非快速眼动（NonREM）睡眠期间增加了 EEG 慢波活动，表明睡眠加深，而与睡眠相关的记忆巩固保持不变。此外，IL-1ra 在睡眠期间略微增加了催乳素并降低了皮质醇水平。IL-1ra 后经典单核细胞产生的 IL-1 减少。与动物研究结果的差异可能反映了物种差异，并强调了在人类中研究细胞因子作用的重要性。
