Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.
Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.
复制标题
DOI：
10.1097/psy.0b013e3181f883ce
复制
发表时间：
2010-11
影响因子：
3.3
通讯作者：
Evans DL
中科院分区：
文献类型：
--
作者：
Benton T;Lynch K;Dubé B;Gettes DR;Tustin NB;Ping Lai J;Metzger DS;Blume J;Douglas SD;Evans DL
为了验证选择性5-羟色胺再摄取抑制剂（SSRI）西酞普兰会下调艾滋病毒感染性的假设，以及在抑郁症患者中观察到的最大效果。抑郁症是艾滋病毒/艾滋病发病率和死亡率的一个危险因素。5-羟色胺（5-HT）神经传递与抑郁症的病理生物学有关，抑郁症的药物治疗靶向该系统。5-HT转运体和5-HT受体广泛分布于中枢神经系统和免疫系统。抑郁症与自然杀伤细胞（NK）细胞和CD 8+淋巴细胞（HIV感染的关键调节因子）的抑制有关。在48名抑郁和非抑郁女性中，使用急性和慢性HIV感染的离体模型来研究西酞普兰对HIV病毒感染和复制的影响。对于急性和慢性感染模型，在西酞普兰治疗条件和对照条件下测量HIV逆转录酶（RT）活性。SSRI在急性和慢性感染模型中均显著下调RT反应。具体而言，西酞普兰显着降低巨噬细胞的急性HIV感染性。西酞普兰也显着降低潜伏感染的T细胞系和潜伏感染的巨噬细胞系中的HIV病毒复制。抑郁状态的下调没有差异。这些研究表明，SSRI增强了HIV/AIDS中NK/CD 8非细胞溶解性HIV抑制，并降低了巨噬细胞的HIV病毒感染性，这表明需要进行体内研究以确定靶向5-羟色胺的药物在宿主防御HIV中的潜在作用。
To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down regulate HIV infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/AIDS. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells (NK) cells and CD8+ lymphocytes, key regulators of HIV infection. Ex-vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication, in 48 depressed and non-depressed women. For both the acute and chronic infection models, HIV reverse transcriptase (RT) activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly downregulated the RT response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances NK/CD8 non-cytolytic HIV suppression in HIV/AIDS and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.