Norman Cousins Center for Psychoneuroimmunology, Los Angeles, USA.
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, 300 UCLA Medical Plaza, Room 2273, Los Angeles, CA, 90095, USA.
Sci Rep. 2022 Jul 24;12(1):12627. doi: 10.1038/s41598-022-16364-3.
Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression. Given epidemiologic relationships identified between IL-6, tumor necrosis factor (TNF)- α, and subsequent depression, levels of these pro-inflammatory cytokines were also explored as potential moderators of depressed mood response to endotoxin. Secondary analyses were completed on data from healthy adults (n = 114) who completed a double-blind, placebo-controlled randomized trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). IL-8, as well as IL-6 and TNF- α, were measured at baseline prior to infusion, and depressed mood and feelings of social disconnection were assessed approximately hourly. Baseline levels of IL-8, but not IL-6 or TNF-α, moderated depressed mood (β = - 0.274, p = .03) and feelings of social disconnection (β = - 0.307, p = .01) responses, such that higher baseline IL-8 was associated with less increase in depressed mood and feelings of social disconnection in the endotoxin, but not placebo, condition. IL-8 had threshold effects, in which highest quartile IL-8 (≥ 2.7 pg/mL) attenuated increases in depressed mood in response to endotoxin as compared to lower IL-8 quartiles (p = .02). These findings suggest that IL-8 may be a biological factor that mitigates risk of inflammation-associated depression. Clinical trials registration: ClinicalTrials.gov NCT01671150, registration date 23/08/2012.
新出现的证据表明白细胞介素 (IL)-8 在抑郁症的背景下具有保护作用。在抑郁患者中，较高水平的 IL-8 与抑郁症状严重程度较低相关，而与治疗相关的 IL-8 增加与抑郁患者的积极反应相关。本研究（一项已完成的随机对照试验的二次分析）旨在研究更高水平的 IL-8 是否可以减轻炎症诱导的抑郁模型引起的抑郁情绪增加。鉴于已确定 IL-6、肿瘤坏死因子 (TNF)-α 与随后的抑郁之间存在流行病学关系，还探讨了这些促炎细胞因子的水平是否可以作为内毒素引起的抑郁情绪反应的潜在调节剂。对完成了一项双盲、安慰剂对照随机试验的健康成年人（n=114）的数据进行了二次分析，参与者被随机分配接受单次低剂量内毒素（源自大肠杆菌；0.8ng/kg 体重）或安慰剂（相同体积的 0.9%生理盐水）输注。在输注前的基线测量了 IL-8 以及 IL-6 和 TNF-α，大约每小时评估一次抑郁情绪和社交脱节感。基线 IL-8 水平（但不是 IL-6 或 TNF-α）调节抑郁情绪（β=-0.274，p=0.03）和社交脱节感（β=-0.307，p=0.01）反应，即基线 IL-8 水平较高与内毒素而非安慰剂条件下抑郁情绪和社交脱节感的增加减少有关。IL-8 具有阈值效应，即最高四分位 IL-8（≥2.7pg/mL）与较低的 IL-8 四分位相比，可减轻内毒素引起的抑郁情绪增加（p=0.02）。这些发现表明，IL-8 可能是减轻与炎症相关的抑郁风险的生物学因素。临床试验注册：ClinicalTrials.gov NCT01671150，注册日期 2012 年 8 月 23 日。
