Castanon Nathalie, Leonard Brian E, Neveu Pierre J, Yirmiya Raz
INRA-INSERM U394, Neurobiologie Integrative, Institut François Magendie, Rue Camille Saint-Saëns, Bordeaux Cedex 33077, France.
Brain Behav Immun. 2002 Oct;16(5):569-74. doi: 10.1016/s0889-1591(02)00008-9.
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 psychoneuroimmunological disorder where a central increase of pro-inflammatory 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.
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脑效应介导的。这些观察结果表明，抑郁症可被视为一种精神神经免疫性疾病，其中促炎细胞因子在中枢的增加可能会对与该疾病症状相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，抗抑郁药的治疗效果至少部分是通过减弱促炎细胞因子在大脑中的表达和/或作用来实现的。尽管存在固有的局限性，但基于与人类观察到的症状的行为和药理学相似性的抑郁症动物模型，是检验这一假设和研究抗抑郁药免疫作用机制的最佳可用工具。用不同类别的抗抑郁药进行治疗确实能预防细胞因子诱导的类似抑郁的生物学和行为变化。这种“抗炎”特性可能是由于促炎/抗炎细胞因子平衡的改变。抗抑郁药这些作用的潜在机制目前尚不清楚，但现有文献提出了几种可能性，包括对代表细胞因子诱导的情绪障碍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视野。它们所显示的免疫作用是副作用还是其临床活性的重要组成部分仍有待阐明。
