UCLA Insomnia Clinic, Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, United States.
Department of Psychiatry and Behavioral Health, Zucker Hillside Hospital at Northwell Health, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, United States.
Brain Behav Immun. 2021 Mar;93:245-253. doi: 10.1016/j.bbi.2021.01.034. Epub 2021 Feb 10.
Chronic inflammation contributes to multiple diseases including cardiovascular diseases, autoimmune disorders, metabolic disorders, and psychiatric conditions. Melatonin, a hormone responsible for circadian rhythm, plays a complex role within the immune system, including having an anti-inflammatory effect. While there are numerous animal studies demonstrating this effect, few human clinical trials have been conducted. This systematic review of clinical trials examined whether exogenous melatonin reduces levels of inflammatory markers in humans. We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO, and the references of the identified articles for randomized and non-randomized placebo-controlled trials. Data were extracted from the articles and meta-analyses were conducted using a random effects model to calculate standardized mean differences (SMDs, i.e., Cohen's d). From an initial search result of 4548 references, 31 studies met the inclusion criteria and were included involving 1517 participants. Melatonin had significant anti-inflammatory effects on interleukin (IL)-1 (SMD -1.64; 95% confidence interval [CI] -2.86, -0.43; p = 0.008), IL-6 (-3.84; -5.23, -2.46; p < 0.001), IL-8 (-21.06; -27.27, -14.85; p < 0.001), and tumor necrosis factor (TNF) (-1.54; -2.49, -0.58; p = 0.002), but not on C-reactive protein (CRP) (-0.18; -0.91, 0.55; p = 0.62). Trimming outlier studies with large effect sizes eliminated publication bias, and summary effect sizes were significant for IL-1 (SMD -1.11; 95% CI -1.90, -0.32; p = 0.006), IL-6 (-1.91; -2.98, -0.83; p = 0.001), and IL-8 (-13.46; -18.88, -8.04; p < 0.001), but not for TNF (-0.45; -1.13, 0.23; p = 0.19). Exogenous melatonin reduced levels of inflammatory markers and may be useful for prevention and adjuvant treatment of inflammatory disorders. Melatonin is safe with few side effects, which makes it an excellent agent for prevention of inflammatory disorders. Because chronic inflammation increases with aging and inflammation plays a role in the etiology of numerous diseases that affect older populations, melatonin has the potential to be widely used particularly in older adults.
慢性炎症会导致多种疾病，包括心血管疾病、自身免疫性疾病、代谢紊乱和精神疾病。褪黑素是一种负责昼夜节律的激素，在免疫系统中发挥着复杂的作用，包括抗炎作用。虽然有许多动物研究表明了这种作用，但很少有人类临床试验进行。本系统评价综述了临床试验，以检验外源性褪黑素是否能降低人类炎症标志物的水平。我们检索了 PubMed、Embase、Cochrane 图书馆、Scopus 和 PsycINFO，并检索了已确定文章的参考文献，以获取随机和非随机安慰剂对照试验。从最初的 4548 条参考文献中，有 31 项研究符合纳入标准，共纳入了 1517 名参与者。褪黑素对白细胞介素 (IL)-1 (SMD -1.64; 95%置信区间 [CI] -2.86, -0.43;p=0.008)、IL-6 (-3.84; -5.23, -2.46;p<0.001)、IL-8 (-21.06; -27.27, -14.85;p<0.001) 和肿瘤坏死因子 (TNF) (-1.54; -2.49, -0.58;p=0.002) 具有显著的抗炎作用，但对 C 反应蛋白 (CRP) (-0.18; -0.91, 0.55;p=0.62) 没有影响。剔除具有较大效应量的离群值研究消除了发表偏倚，综合效应量对 IL-1 (SMD -1.11; 95% CI -1.90, -0.32;p=0.006)、IL-6 (-1.91; -2.98, -0.83;p=0.001) 和 IL-8 (-13.46; -18.88, -8.04;p<0.001) 有显著影响，但对 TNF (-0.45; -1.13, 0.23;p=0.19) 没有影响。外源性褪黑素降低了炎症标志物的水平，可能对预防和辅助治疗炎症性疾病有用。褪黑素安全性好，副作用少，是预防炎症性疾病的理想药物。由于慢性炎症随年龄增长而增加，而炎症在影响老年人群的许多疾病的发病机制中发挥作用，因此褪黑素具有广泛应用的潜力，特别是在老年人中。
