Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
Brain Behav Immun. 2011 Oct;25(7):1416-26. doi: 10.1016/j.bbi.2011.04.011. Epub 2011 Apr 23.
The sleep-wake cycle is characterized by complex interactions among the central nervous, the endocrine and the immune systems. Continuous 24-h wakefulness prevents sleep-associated hormone regulation resulting in impaired pro-inflammatory cytokine production. Importantly, cytokines and hormones also modulate the complement system, which in turn regulates several adaptive immune responses. However, it is unknown whether sleep affects the activation and the immunoregulatory properties of the complement system. Here, we determined whether the 24-h sleep-wake cycle has an impact on: (i) the levels of circulating complement factors; and (ii) TLR4-mediated IL-12 production from human IFN-γ primed monocytes in the presence or absence of C5a receptor signaling. For this purpose, we analyzed the blood and blood-derived monocytes of 13 healthy donors during a regular sleep-wake cycle in comparison to 24 h of continuous wakefulness. We found decreased plasma levels of C3 and C4 during nighttime hours that were not affected by sleep. In contrast, sleep was associated with increased complement activation as reflected by elevated C3a plasma levels during nighttime sleep. Sleep deprivation prevented such activation. At the cellular level, C5a negatively regulated TLR4-mediated IL-12p40 and p70 production from human monocytes. Importantly, this regulatory effect of C5a on IL-12p70 production was effective only during daytime hours. Thus, similar to hormones, some complement factors and immunoregulatory properties of C5a are influenced by sleep and the circadian rhythm. Our findings that continuous wakefulness has a negative impact on complement activation may provide a rationale for the immunosupportive functions of sleep.
睡眠-觉醒周期的特征是中枢神经系统、内分泌系统和免疫系统之间的复杂相互作用。持续 24 小时的清醒会阻止与睡眠相关的激素调节，导致促炎细胞因子的产生受损。重要的是，细胞因子和激素也调节补体系统，而补体系统反过来又调节几种适应性免疫反应。然而，目前尚不清楚睡眠是否会影响补体系统的激活和免疫调节特性。在这里，我们确定 24 小时的睡眠-觉醒周期是否会对以下方面产生影响：(i) 循环补体因子的水平；以及 (ii) 在 C5a 受体信号存在或不存在的情况下，TLR4 介导的来自人 IFN-γ 预刺激单核细胞的 IL-12 产生。为此，我们在正常睡眠-觉醒周期期间和 24 小时连续清醒期间分析了 13 名健康供体的血液和血液来源的单核细胞。我们发现夜间 C3 和 C4 的血浆水平下降，但睡眠不受影响。相比之下，睡眠与夜间睡眠期间 C3a 血浆水平升高有关，这表明补体激活增加。睡眠剥夺可阻止这种激活。在细胞水平上，C5a 负调节 TLR4 介导的人单核细胞中 IL-12p40 和 p70 的产生。重要的是，C5a 对 IL-12p70 产生的这种调节作用仅在白天有效。因此，与激素类似，一些补体因子和 C5a 的免疫调节特性受睡眠和昼夜节律的影响。我们的发现表明，连续的清醒对补体激活有负面影响，这可能为睡眠的免疫支持功能提供了依据。
