Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor α and interleukin-6
Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor α and interleukin-6
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DOI：
10.1016/j.psychres.2004.01.014
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发表时间：
2005-04-30
影响因子：
11.3
通讯作者：
Lason, W
中科院分区：
文献类型：
--
作者：
Kubera, M;Maes, M;Lason, W
5-羟色胺（5-HT）是一种神经递质和免疫调节剂。5-HT对人巨噬细胞和淋巴细胞产生细胞因子的影响认识不足。在这篇文章中，我们研究了5-HT的作用。调节两种促炎细胞因子，即白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF α）的产生，以及5-HT 1A和5-HT 2受体在该过程中的作用。具体的目的是检查5-HT、对氯苯丙氨酸（PCPA）（一种5-HT消耗剂）、flesinoxan（一种5-HT 1A激动剂）、间氯苯哌嗪（mCPP）（一种5-HT 2B/2C激动剂）和利坦色林（一种5-HT 2A/2C拮抗剂）对上述细胞因子产生的影响。我们发现：（1）5-HT（15 μ g/ml）显著降低IL-6和TNF α的产生;（2）pCPA（5 μ M）显著抑制IL-6和TNF α的产生;（3）mCPP（2.7 μ g/ml）显著增加IL-6和TNF α的产生。结论：细胞内5-HT对IL-6和TNF α的最佳合成是必需的;生理浓度的5-HT可通过刺激5-HT 2受体增加IL-6和TNF α的产生;细胞外5-HT浓度高于基线生理水平可抑制上述细胞因子的产生。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Serotonin (5-HT) is a neurotransmitter and immune modulator. The effect of 5-HT on the production of cytokines by human macrophages and lymphocytes is poorly recognized. In the present article we examine the role of 5-HT in. modulating the production of two pro-inflammatory cytokines, i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha), as well as the role of 5-HT1A and 5-HT2 receptors in this process. The specific aims were to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan, a 5-HT1A agonist, m-chlorophenylpiperazine (mCPP), a 5-HT2B/2C agonist, and ritanserin, a 5-HT2A/2C antagonist, on the production of the above cytokines. We found that: (1) 5-HT, 15 mu g/ml, significantly decreased IL-6 and TNF alpha production; (2) pCPA, 5 mu M, significantly suppressed the production of IL-6 and TNF alpha; and (3) mCPP, 2.7 mu g/ml, significantly increased the production of IL-6 and TNF alpha. It is concluded that intracellular 5-HT is necessary for optimal synthesis of IL-6 and TNFot; 5-HT in physiological concentrations may increase IL-6 and TNFa production by stimulating 5-HT2 receptors; and extracellular 5-HT concentrations above the baseline physiological levels may suppress the production of the above cytokines. (c) 2005 Elsevier Ireland Ltd. All rights reserved.