Department of Research, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan.
Int Immunopharmacol. 2012 Jan;12(1):197-204. doi: 10.1016/j.intimp.2011.11.011. Epub 2011 Dec 5.
Antipsychotic drugs (APDs) that bind mainly to the dopamine D2 receptor or the type II 5-HT receptor have been used to ease the symptoms of schizophrenia. Several studies have reported that APDs can also regulate the immune response. Dendritic cells (DCs) are the major antigen-presenting cells in the immune system. DCs can release 5-HT and dopamine to modulate T-cell activation and differentiation. In this study, we use the monocyte-derived DCs to investigate the drug effects of typical APD (haloperidol) and atypical APD (risperidone) on DCs in vitro. Our studies revealed that only risperidone but not haloperidol affected the cytokine and chemokine production of mature DCs. Risperidone increased the production of IL-10 and MDC as well as the proinflammatory cytokines, such as IL-6, IL-8, and TNF-α, but decreased the production of IP-10 and IL-12. Furthermore, the exposure of DCs to risperidone led to lower IFN-γ production by T-cells. The results suggested that risperidone can modulate the DCs' immune function by inhibiting the potent Th1 cytokines and increasing the potent Th2 cytokines. In addition, the production of TNF-α by risperidone-treated mature DCs will induce the death of neutrophils.
抗精神病药物（APD）主要与多巴胺 D2 受体或 5-HT2 型受体结合，用于缓解精神分裂症的症状。有几项研究报告称，APD 还可以调节免疫反应。树突状细胞（DC）是免疫系统中的主要抗原呈递细胞。DC 可以释放 5-HT 和多巴胺来调节 T 细胞的激活和分化。在这项研究中，我们使用单核细胞来源的 DC 来研究典型 APD（氟哌啶醇）和非典型 APD（利培酮）对体外 DC 的药物作用。我们的研究表明，只有利培酮而不是氟哌啶醇影响成熟 DC 的细胞因子和趋化因子的产生。利培酮增加了 IL-10 和 MDC 的产生以及促炎细胞因子，如 IL-6、IL-8 和 TNF-α，但降低了 IP-10 和 IL-12 的产生。此外，DC 暴露于利培酮会导致 T 细胞产生的 IFN-γ 减少。结果表明，利培酮可以通过抑制强效 Th1 细胞因子和增加强效 Th2 细胞因子来调节 DC 的免疫功能。此外，利培酮处理的成熟 DC 产生的 TNF-α会诱导中性粒细胞死亡。
