MacCormack Jennifer K, Gaudier-Diaz Monica M, Armstrong-Carter Emma L, Arevalo Jesusa M G, Meltzer-Brody Samantha, Sloan Erica K, Cole Steven W, Muscatell Keely A
Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Neuropsychopharmacology. 2021 Mar;46(4):756-762. doi: 10.1038/s41386-020-00897-0. Epub 2021 Jan 15.
Dysregulation of the immune system is one potential mechanism by which acute stress may contribute to downstream disease etiology and psychopathology. Here, we tested the role of β-adrenergic signaling as a mediator of acute stress-induced changes in immune cell gene expression. In a randomized, double-blind, and placebo-controlled trial, 90 healthy young adults (44% female) received a single 40 mg dose of the β-blocker propranolol (n = 43) or a placebo (n = 47) and then completed the Trier Social Stress Test (TSST). Pre- and post-stress blood samples were assayed for prespecified sets of pro-inflammatory and antiviral/antibody gene transcripts. Analyses revealed increased expression of both inflammatory and antiviral/antibody-related genes in response to the TSST, and these effects were blocked by pre-treatment with propranolol. Bioinformatics identified natural killer cells and dendritic cells as the primary cellular context for transcriptional upregulation, and monocytes as the primary cellular carrier of genes downregulated by the TSST. These effects were in part explained by acute changes in circulating cell types. Results suggest that acute psychosocial stress can induce an "acute defense" molecular phenotype via β-adrenergic signaling that involves mobilization of natural killer cells and dendritic cells at the expense of monocytes. This may represent an adaptive response to the risk of acute injury. These findings offer some of the first evidence in humans that β-blockade attenuates psychosocial stress-induced increases in inflammatory gene expression, offering new insights into the molecular and immunologic pathways by which stress may confer risks to health and well-being.
免疫系统失调是急性应激可能导致下游疾病病因和精神病理学的一种潜在机制。在此，我们测试了β-肾上腺素能信号传导作为急性应激诱导免疫细胞基因表达变化的介导因子的作用。在一项随机、双盲、安慰剂对照试验中，90名健康的年轻成年人（44%为女性）接受了单次40毫克剂量的β受体阻滞剂普萘洛尔（n = 43）或安慰剂（n = 47），然后完成了特里尔社会应激测试（TSST）。对应激前后的血样进行了预指定的促炎和抗病毒/抗体基因转录本检测。分析显示，对TSST的反应中，炎症和抗病毒/抗体相关基因的表达均增加，而这些效应被普萘洛尔预处理所阻断。生物信息学确定自然杀伤细胞和树突状细胞是转录上调的主要细胞背景，单核细胞是TSST下调基因的主要细胞载体。这些效应部分由循环细胞类型的急性变化所解释。结果表明，急性心理社会应激可通过β-肾上腺素能信号传导诱导一种“急性防御”分子表型，该表型涉及自然杀伤细胞和树突状细胞的动员，以单核细胞为代价。这可能代表了对急性损伤风险的一种适应性反应。这些发现为人类提供了一些初步证据，表明β受体阻滞剂可减轻心理社会应激诱导的炎症基因表达增加，为应激可能给健康和幸福带来风险的分子和免疫途径提供了新的见解。
