Dimitrov Stoyan, Lange Tanja, Nohroudi Klaus, Born Jan
Department of Neuroendocrinology, University of Lübeck, Germany.
Sleep. 2007 Apr;30(4):401-11. doi: 10.1093/sleep/30.4.401.
There is evidence that sleep facilitates the adaptive immune response to infectious agents and, thereby, supports immunologic memory. The effect might be attained by sleep-induced changes in the number and function of dendritic cells (DCs), which play a key role in the initiation of the immune response. This study aimed to dissociate effects of sleep and circadian rhythm on circulating numbers of DC precursors, ie, CD14+CD16- and CD14(dim)CD16+ monocytes, myeloid dendritic cell precursors (pre-mDC), and plasmacytoid dendritic cells (PDC) and on 2 key cytokines produced by these cells, ie, interleukin (IL)-12 and interferon (IFN)-alpha.
In a within-subject cross-over design, human subjects were examined on 2 occasions, ie, during a normal sleep-wake cycle and during 24 hours of wakefulness. Blood was sampled every 1.5 hours during nighttime and every 3 hours during daytime.
Experiments took place under controlled laboratory conditions.
Twenty-seven healthy men aged between 18 and 30 years.
Compared with wakefulness, sleep was associated with a striking increase in the number of pre-mDC producing IL-12, which is a main inducer of Th1 responses. In addition, sleep slightly decreased PDC and also T cell counts but did not affect IFN-alpha production by PDC. Sleep, however, substantially decreased numbers of CD14(dim)CD16+ monocytes, probably reflecting increased margination of the cells upon a sleep-related drop in catecholamine release.
Our data identify pre-mDC producing IL-12 as a basic target of sleep that is most closely related to mature APC function and whereby sleep can effectively enhance adaptive immune responses.
有证据表明,睡眠有助于机体对感染因子产生适应性免疫反应,从而支持免疫记忆。这种作用可能是通过睡眠引起的树突状细胞(DCs)数量和功能的变化来实现的,而树突状细胞在免疫反应的启动中起着关键作用。本研究旨在区分睡眠和昼夜节律对循环中DC前体细胞数量的影响,即CD14+CD16-和CD14(dim)CD16+单核细胞、髓样树突状细胞前体(pre-mDC)和浆细胞样树突状细胞(pDC),以及对这些细胞产生的两种关键细胞因子,即白细胞介素(IL)-12和干扰素(IFN)-α的影响。
采用受试者自身交叉设计,对人类受试者进行了两次检查,即在正常睡眠-觉醒周期和24小时清醒期间。夜间每1.5小时采集一次血液,白天每3小时采集一次。
实验在受控的实验室条件下进行。
27名年龄在18至30岁之间的健康男性。
与清醒状态相比,睡眠与产生IL-12的pre-mDC数量显著增加有关,IL-12是Th1反应的主要诱导因子。此外,睡眠使pDC和T细胞计数略有下降,但不影响pDC产生IFN-α。然而,睡眠使CD14(dim)CD16+单核细胞数量大幅减少,这可能反映了睡眠相关的儿茶酚胺释放下降导致细胞边缘化增加。
我们的数据确定产生IL-12的pre-mDC是睡眠的一个基本靶点,它与成熟的抗原呈递细胞功能最密切相关,睡眠可通过该靶点有效增强适应性免疫反应。