Department of Research, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan.
Immunol Lett. 2011 Oct 30;140(1-2):81-91. doi: 10.1016/j.imlet.2011.06.011. Epub 2011 Jul 6.
Antipsychotic drugs (APDs) are commonly used to ease the symptoms of schizophrenia; however, these same drugs also have an effect on the human immune system. Our previous studies have shown that risperidone and clozapine effectively decrease the production of IFN-γ for CD4(+) T-cells in PBMC. In contrast, haloperidol causes an increase in the production of IFN-γ for CD4(+) T-cells in PBMC. In this study we show that risperidone and clozapine can reduce Th1 cell differentiation and T-bet expression. The differentiation of Th1 cells was reduced in clozapine or risperidone treated PBMC by inhibiting the phosphorylation of AKT but not STAT-4. Typical APD, haloperidol, had the opposite effect in regulating T cell differentiation when compared with atypical APDs including risperidone and clozapine. Haloperidol decreased the expression of GATA-3, a Th2-related transcription factor, by inhibiting NF-κB activation rather than STAT-6 phosphorylation and thus decreased Th2 differentiation. In addition, chronic risperidone and clozapine treatment reduces the IFN-γ producing CD4(+) T-cell population within PBMC. In conclusion, this study suggests that APDs do indeed regulate the body's immune response and therefore all APDs should have their own patent in regulating immune responses.
抗精神病药物（APD）通常用于缓解精神分裂症的症状；然而，这些药物也会对人体免疫系统产生影响。我们之前的研究表明，利培酮和氯氮平能有效降低 PBMC 中 CD4+T 细胞产生 IFN-γ。相比之下，氟哌啶醇会导致 PBMC 中 CD4+T 细胞产生 IFN-γ增加。在这项研究中，我们表明利培酮和氯氮平可以减少 Th1 细胞分化和 T-bet 表达。在 clozapine 或 risperidone 处理的 PBMC 中，Th1 细胞的分化通过抑制 AKT 的磷酸化而不是 STAT-4 的磷酸化而减少。与典型的 APD 相比，包括利培酮和氯氮平在内的非典型 APD 具有相反的调节 T 细胞分化的作用。氟哌啶醇通过抑制 NF-κB 激活而不是 STAT-6 磷酸化来降低 Th2 相关转录因子 GATA-3 的表达，从而减少 Th2 分化。此外，慢性利培酮和氯氮平治疗会减少 PBMC 中产生 IFN-γ的 CD4+T 细胞群体。总之，这项研究表明，APD 确实会调节人体的免疫反应，因此所有的 APD 都应该有自己的专利来调节免疫反应。
