Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome
Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome
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DOI：
10.1016/j.biopsych.2007.08.012
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发表时间：
2008-05-01
影响因子：
10.6
通讯作者：
Douglas, Steven D.
中科院分区：
文献类型：
--
作者：
Evans, Dwight L.;Lynch, Kevin G.;Douglas, Steven D.
背景资料：自然杀伤（NK）细胞在先天免疫中起重要作用，并参与宿主对人类免疫缺陷病毒（HIV）感染的防御。本研究探讨了潜在的作用，三个基本的监管系统，已在调查中的中枢神经系统的研究以及免疫和病毒的研究：血清素，神经激肽，和糖皮质激素systems.Methods：51名HIV-血清阳性受试者被招募到抑郁症和非抑郁症的妇女，以实现一个有代表性的样本。选择性5-羟色胺再摄取抑制剂（SSRI）、P物质（SP）拮抗剂和糖皮质激素拮抗剂对NK细胞功能的影响在来自每个HIV血清阳性受试者的外周血单个核细胞的一系列离体实验中进行了评估。糖皮质激素拮抗剂RU 486对NK细胞毒活性无影响。我们的研究结果表明，这三种药物的影响没有不同的功能depressory.Conclusions：我们的研究结果提供的证据表明，NK细胞在HIV感染的功能可能会增强5-羟色胺再摄取抑制和P物质拮抗。它仍然有待确定，如果HIV相关的损害不仅在NK细胞溶解活性，但也NK noncytolytic活性可以改善SSRI或SP拮抗剂。临床研究是必要的，以解决这些问题和潜在的作用，β-胡萝卜素能药物和SP拮抗剂在提高NK细胞免疫，延缓HIV疾病的进展，并延长生存与HIV感染。
Background: Natural killer (NK) cells play an important role in innate immunity and are involved in the host defense against human immunodeficiency virus (HIV) infection. This study examines the potential role of three underlying regulatory systems that have been under investigation in central nervous system research as well as immune and viral research: serotonin, neurokinin, and glucocorticoid systems.Methods: Fifty-one HIV-seropositive subjects were recruited to achieve a representative sample of depressed and nondepressed women. The effects of a selective serotonin reuptake inhibitor (SSRI), a substance P (SP) antagonist, and a glucocorticoid antagonist on NK cell function were assessed in a series of ex vivo experiments of peripheral blood mononuclear cells from each HIV-seropositive subject.Results: Natural killer cell cytolytic activity was significantly increased by the SSRI citalopram and by the substance P antagonist CP-96345 relative to control conditions; the glucocorticoid antagonist, RU486, showed no effect on NK cytotoxicity. Our results suggest that the effects of the three agents did not differ as a function of depression.Conclusions: Our findings provide evidence that NK cell function in HIV infection may be enhanced by serotonin reuptake inhibition and by substance P antagonism. It remains to be determined if HIV-related impairment in not only NK cytolytic activity but also NK noncytolytic activity can be improved by an SSRI or an SP antagonist. Clinical studies are warranted to address these questions and the potential roles of serotonergic agents and SP antagonists in improving NK cell immunity, delaying HIV disease progression, and extending survival with HIV infection.