Negative immunoregulatory effects of antidepressants:: Inhibition of interferon-γ and stimulation of interleukin-10 secretion

Negative immunoregulatory effects of antidepressants:: Inhibition of interferon-γ and stimulation of interleukin-10 secretion
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DOI:
10.1016/s0893-133x(98)00088-8
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发表时间:
1999-04-01
影响因子:
7.6
通讯作者:
Scharpé, S
Scharpé, S
中科院分区:
医学1区
文献类型:
--
作者:
Maes, M;Song, C;Scharpé, S

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现在有一些证据表明,重度抑郁症伴随着炎症反应系统的激活。也有一些证据表明,抗抑郁药物可以抑制激活的单核细胞释放细胞因子,如IL-1β和IL-6,以及激活的T细胞释放IL-2和干扰素-γ。本研究旨在观察氯丙咪嗪、舍曲林和曲唑酮对促炎细胞因子干扰素-γ和负性免疫调节细胞因子IL-10刺激产生的影响。9名健康志愿者的全血分别用5 mU g/m L的PHA和内毒素、25 mU g/m L的氯丙咪嗪、10(-6)和10(-9)M的氯丙咪嗪、10(-6)和10(-8)M的舍曲林、10(-6)和10(-8)M的曲唑酮刺激72小时,3种抗抑郁药均可显著降低干扰素-γ的分泌,而氯丙咪嗪和舍曲林则显著增加培养上清液中IL-10的分泌。三种抗抑郁药均显著降低干扰素-γ/IL-10比值。结果提示,在治疗浓度范围内,抗抑郁药通过抑制干扰素-γ和刺激IL-10的释放而产生负性免疫调节作用。[神经精神药理学20:370-379,1999](C)1999美国神经心理学学院。爱思唯尔科学公司出版。
There is now some evidence that major depression is accompanied by activation of the inflammatory response system. There is also some evidence that antidepressants may suppress the release of cytokines, such as interleukin-1 beta (IL-2 beta) and IL-6 by activated monocytes and IL-2 and interferon-gamma (IFN gamma) by activated T cells. This study was carried out to examine the effects of clomipramine, sertraline, and trazodone on the stimulated production of IFN gamma, a pro-inflammatory cytokine, and IL-10, a negative immunoregulatory cytokine. Whole blood of nine healthy volunteers was stimulated with PHA, 5 mu g/mL and LPS, 25 mu g/mL for 72 hr with and without incubation with clomipramine, 10(-6) and 10(-9) M, sertraline, 10(-6) and 10(-8) M, and trazodone, 10(-6) and 10(-8) M. All three anti-depressants significantly reduced IFN gamma secretion, whereas clomipramine and sertraline significantly increased IL-10 secretion in culture supernatant. All three antidepressants significantly reduced the IFN gamma/IL-10 ratio. The results suggest that antidepressants, at concentrations in the therapeutical range, have negative immunoregulatory effects through inhibition of IFN gamma and stimulation of IL-10 release. [Neuropsychopharmacology 20:370-379, 1999] (C) 1999 American College of Neuropsychology. Published by Elsevier Science Inc.