Shift of monocyte function toward cellular immunity during sleep

Shift of monocyte function toward cellular immunity during sleep
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DOI:
10.1001/archinte.166.16.1695
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发表时间:
2006-09-18
影响因子:
--
通讯作者:
Born, Jan
Born, Jan
中科院分区:
其他
文献类型:
--
作者:
Lange, Tanja;Dimitrov, Stoyan;Born, Jan

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背景:睡眠被认为可以增强免疫防御。我们假设睡眠通过将 1 型和 2 型细胞因子活性之间的平衡转向增加 1 型活性来实现这种效果,从而支持适应性细胞免疫反应。方法:我们通过多参数流式细胞术对健康人体受试者 (n=11) 在定期睡眠-觉醒周期和 24 小时清醒期间分析单核细胞衍生的 1 型(白细胞介素 12 [IL-12])和 2 型 (IL-10) 细胞因子。结果:睡眠增加产生 IL-12 的单核细胞数量,同时减少产生 IL-10 的单核细胞数量,从而在这些细胞中诱导清晰的节律,最大数量分别出现在凌晨 2:20 和 11:30。在持续清醒期间,节奏完全消失。相关分析和补充体外研究表明,高催乳素和低皮质醇水平是导致睡眠期间 IL-12/IL-10 比率向 IL-12 活性增加方向转变的因素。结论:单核细胞来源的 IL-12 和 IL-10 在调节抗原呈递细胞和淋巴细胞之间的突触方面发挥着关键作用。通过优先支持 1 型 IL-12 活性,睡眠会诱导主要 1 型和 2 型细胞因子之间 24 小时的振荡,从而在整体上提高适应性免疫反应的功效。改善睡眠可能是一种治疗选择,可提高疫苗接种的成功率和治疗以 2 型细胞因子过度活跃为特征的疾病(例如特应性皮炎和人类免疫缺陷病毒感染)的成功率。
Background: Sleep is considered to strengthen immune defense. We hypothesized that sleep achieves this effect by shifting the balance between types 1 and 2 cytokine activity toward increased type 1 activity, thereby supporting adaptive cellular immune responses.Methods: We analyzed monocyte-derived type 1 ( interleukin 12 [IL-12]) and type 2 (IL-10) cytokines by means of multiparametric flow cytometry in healthy human subjects (n=11) during a regular sleep-wake cycle and 24 hours of wakefulness.Results: Sleep increased the number of IL-12 producing monocytes and concurrently decreased the number of IL-10-producing monocytes, thereby inducing clear rhythms in these cells, with maximum numbers at 2: 20 and 11: 30 AM, respectively. The rhythms were completely absent during continuous wakefulness. Correlation analyses and supplementary in vitro studies suggest that high prolactin and low cortisol levels are factors contributing to the shift in the IL-12/IL-10 ratio toward increased IL-12 activity during sleep.Conclusions: Monocyte-derived IL-12 and IL-10 play a critical role for tuning the synapse between antigen-presenting cells and lymphocytes. By preferentially supporting type 1 IL-12 activity, sleep induces a 24-hour oscillation between predominant types 1 and 2 cytokines and, in this way, acts to globally increase the efficacy of adaptive immune responses. Improving sleep could represent a therapeutic option to enhance the success of vaccinations and success in the treatment of diseases (eg, atopic dermatitis and human immunodeficiency virus infection) that are characterized by type 2 cytokine overactivity.