Effects of antidepressants on cytokine production and actions
Effects of antidepressants on cytokine production and actions
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DOI：
10.1016/s0889-1591(02)00008-9
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发表时间：
2002-10-01
影响因子：
15.1
通讯作者：
Yirmiya, R
中科院分区：
文献类型：
--
作者：
Castanon, N;Leonard, BE;Yirmiya, R
抑郁症的许多特征与对感染的生理和行为反应之间存在着有趣的相似之处，这些反应是由细胞因子的大脑效应介导的。这些观察结果表明，抑郁症可以被认为是一种精神神经免疫疾病，其中促炎细胞因子的集中增加可能对与该疾病症状有关的神经化学和神经内分泌系统的功能活动产生不利影响。根据这一假设，抗抑郁药的治疗作用至少部分是通过减弱促炎细胞因子的脑表达和/或作用来发挥的。尽管有其固有的局限性，但基于行为和药理学与人类观察到的症状的类比的抑郁症动物模型代表了检验这一假设和研究抗抑郁药免疫作用作用机制的最佳可用工具。使用不同类别的抗抑郁药治疗确实可以预防细胞因子诱导的抑郁样生物学和行为变化。这种“抗炎”特征可能是由于促炎/抗炎细胞因子平衡的改变所致。抗抑郁药产生这些作用的机制目前尚不清楚，但现有文献提出了几种可能性，包括对代表细胞因子引起的情绪障碍的潜在介质的不同分子的作用。本综述中总结的研究为抑郁症的病理生理学和抗抑郁药的药理学开辟了新的前景。它们所表现出的免疫作用是副作用还是其临床活性的重要部分仍有待阐明。 (C) 2002 年爱思唯尔科学（美国）。版权所有。
There are intriguing analogies between many features of depression and physiological and behavioral responses to infection, which are mediated by the brain effects of cytokines. These observations suggest that depression can be considered as a psychoneurointmunological disorder where a central increase of proinflammatory cytokines, may have adverse consequences on the functional activity of the neurochemical and neuroendocrine systems implicated in the symptoms of the disorder. According to this hypothesis, the therapeutic effects of antidepressants should be at least partly exerted by attenuating the brain expression and/or actions of pro-inflammatory cytokines. Despite their inherent limitations, animal models of depression that are based on behavioral and pharmacological analogies with the symptoms observed in humans, represent the best available tool to test this hypothesis and to investigate the action mechanisms of the immune effects of antidepressants. Treatment with different classes of antidepressants indeed conferred protection against cytokine-induced depressive-like biological and behavioral changes. This 'anti-inflammatory' profile may be due to alterations of the pro-/anti-inflammatory cytokine balance. The mechanisms underlying these effects of antidepressants are presently unknown, but the available literature suggests several possibilities, including actions on different molecules representing potential mediators of mood disorders induced by cytokines. The studies summarized in this review have opened up new vistas in both the pathophysiology of depression and the pharmacology of antidepressants. Whether their demonstrated immune effects are a side effect or a significant part of their clinical activity still remains to be elucidated. (C) 2002 Elsevier Science (USA). All rights reserved.