Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans
Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans
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DOI：
10.1016/j.bbi.2003.08.004
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发表时间：
2004-07-01
影响因子：
15.1
通讯作者：
Born, J
中科院分区：
文献类型：
--
作者：
Dimitrov, S;Lange, T;Born, J
最近的人类研究表明，有规律的夜间睡眠对实验性感染(疫苗接种)的免疫反应具有支持性影响。我们在这里假设，睡眠可以通过将辅助性T细胞1(Th1)和辅助性T细胞2(Th2)之间的细胞因子活性的平衡转向Th1主导，从而有利于细胞而不是体液对感染的反应。我们采用受试者内交叉设计，比较了14名健康男性在有规律的夜间睡眠(23：00至07：00小时)和在相同的夜间时段保持清醒时的Th1/Th2细胞因子平衡。每隔2 h采血一次，用多参数流式细胞仪在单细胞水平检测T细胞衍生细胞因子干扰素-γ(IFN-γ)、白介素2(IL-2)、白介素4(IL-4)和肿瘤坏死因子-α(JNF-α)的产生。此外，还检测了几种免疫活性激素-催乳素、生长激素(GH)、促甲状腺激素(TSH)、皮质醇和褪黑素-已知它们的释放受睡眠的调节。与清醒状态相比，早期夜间睡眠导致Th1/Th2细胞因子平衡向Th1活性增加转变，表现为产生干扰素-γ/IL-4的辅助性T细胞比率增加(p<；0.05)。然而，Th1的改变只是中等大小，并在睡眠后期被Th2主导(p<；0.05)所取代。它可能是通过释放催乳素和生长激素来实现的，这两种激素在睡眠中都明显增加(p<；.001)。尽管出乎意料，但睡眠对T细胞细胞因子产生的最显著影响是产生肿瘤坏死因子-α的CD8+细胞显著减少，这可能反映了细胞毒效应细胞和记忆T细胞的外渗增加。(C)2004 Elsevier Inc.保留所有权利。
Recent human studies suggested a supportive influence of regular nocturnal sleep on immune responses to experimental infection (vaccination). We hypothesized here that sleep could case such responses by shifting the balance between T helper 1 (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby favoring cellular over humoral responses to infection. We compared the Th1/Th2 cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00 and 07:00 h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design. Blood was collected every 2 h. Production of T cell derived cytokines-interferon-gamma (IFN-gamma), interleukin-2 (lL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha JNF-alpha was measured at the single cell level using multiparametric flow cytometry. Also, several immunoactive hormones-prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), cortisol, and melatonin-were measured, the release of which is known to be regulated by sleep. Compared with wakefulness, early nocturnal sleep induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity, as indicated by an increased (p < .05) ratio of IFN-gamma/IL-4 producing T helper cells. However, the Th1 shift was only of moderate size and replaced by Th2 dominance during late sleep (p < .05). It could be mediated via release of prolactin and GH which both were distinctly increased during sleep (p < .001). Though unexpected, the most pronounced effect of sleep on T cell cytokine production was a robust decrease in TNF-alpha producing CD8+ cells probably reflecting increased extravasation of cytotoxic effector and memory T cells. (C) 2004 Elsevier Inc. All rights reserved.