Maes Michael
Clinical Research Centre for Mental Health, Antwerp, Belgium.
Hum Psychopharmacol. 2001 Jan;16(1):95-103. doi: 10.1002/hup.191.
There is some evidence that major depression is accompanied by activation of the inflammatory-response system (IRS). It has been hypothesized that increased production of proinflammatory cytokines may play a role in the etiology of major depression. If increased production of proinflammatory cytokines is at all involved in the etiology of depression, one would expect antidepressive treatments to have negative immunoregulatory effects. This paper reviews the effects of antidepressants, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), heterocyclic antidepressants (HCAs), serotonin-noradrenaline reuptake inhibitors (SNRIs), lithium, l-5-hydroxytroptophan (L-5-HTP), reversible inhibitors of MAO-A (RIMA) on the production of proinflammatory cytokines, e.g. interferon-gamma (IFNgamma), and negative immunoregulatory cytokines and agents, e.g. interleukin-10 (IL-10). In depressed patients, prolonged treatment with antidepressants and mood stabilizers normalizes signs of activation of the IRS, such as increased serum IL-6 and acute phase protein concentrations. In vitro, it has been shown that various types of antidepressive drugs, including TCAs (imipramine; clomipramine); SSRIs (citalopram, fluoxetine, sertraline); lithium; SNRIs (venlafaxine); HCAs (trazodone); RIMAs (moclobemide) and L-5-HTP significantly suppress the ratio of IFNgamma/IL-10 production by peripheral blood immunocytes. These antidepressant drugs appear to have a common effect on the IRS, i.e. in vitro they increase the production of IL-10 by peripheral blood leukocytes. Thus, the results suggest that antidepressants have negative immunoregulatory effects. It may be speculated that antidepressants exert some of their antidepressant effects through their negative immunoregulatory capacities. Copyright 2001 John Wiley & Sons, Ltd.
有证据表明，重度抑郁症伴有炎症反应系统（IRS）的激活。据推测，促炎细胞因子产生增加可能在重度抑郁症的病因中起作用。如果促炎细胞因子产生增加确实参与了抑郁症的病因，那么人们会预期抗抑郁治疗具有负性免疫调节作用。本文综述了三环类抗抑郁药（TCA）、选择性5-羟色胺再摄取抑制剂（SSRI）、杂环类抗抑郁药（HCA）、5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）、锂盐、L-5-羟色氨酸（L-5-HTP）、单胺氧化酶-A可逆抑制剂（RIMA）等抗抑郁药对促炎细胞因子如γ-干扰素（IFNγ）产生的影响，以及对负性免疫调节细胞因子和物质如白细胞介素-10（IL-10）的影响。在抑郁症患者中，长期使用抗抑郁药和心境稳定剂可使IRS激活的指标正常化，如血清IL-6和急性期蛋白浓度升高。在体外实验中，已表明包括TCA（丙咪嗪；氯米帕明）、SSRI（西酞普兰、氟西汀、舍曲林）、锂盐、SNRI（文拉法辛）、HCA（曲唑酮）、RIMA（吗氯贝胺）和L-5-HTP在内的各种抗抑郁药可显著抑制外周血免疫细胞产生IFNγ/IL-10的比例。这些抗抑郁药似乎对IRS有共同作用，即在体外它们可增加外周血白细胞产生IL-10。因此，结果提示抗抑郁药具有负性免疫调节作用。可以推测，抗抑郁药通过其负性免疫调节能力发挥部分抗抑郁作用。版权所有2001约翰威立父子有限公司。
