Mental Health Research Center, Moscow, Russia.
J Neuroimmune Pharmacol. 2019 Sep;14(3):369-374. doi: 10.1007/s11481-019-09860-3. Epub 2019 Jul 6.
It is known that psychotropic substances affect the immune system. Unfortunately, chronic antipsychotic administration causes side toxicological effects, associated with oxidative stress. The mechanisms of these effects are still unclear. We investigated the impact of sub-chronic administration of haloperidol (Hal) on parameters of innate immunity and related systems in healthy rats and compared them with Hal content. Hal administration (0.5 mg/kg, 3 weeks) resulted in two-fold decrease of the activity of the complement system and hemostasis. Hal content correlated with the activity of the complement (r = -0.71), phagocytic activity of peritoneal macrophages (r = 0.78), leukocyte elastase (r = -0.71) and glutathione-S-transferase activity (r = -0.67). Hal fully blocked in vitro PMA-induced iNOS expression in macrophages and changed their morphology to "anti-inflammatory" phenotype. The comparison of in vivo and in vitro data showed that Hal has a direct effect on phagocytic component of innate immunity and an indirect effect on leukocyte elastase and antioxidant enzymes. The results obtained in the present study indicated that Hal significantly affects homeostasis and causes a number of complex biological transformations. Graphical Abstract.
已知精神药物会影响免疫系统。不幸的是，慢性抗精神病药物治疗会引起与氧化应激相关的毒性副作用。这些影响的机制尚不清楚。我们研究了亚慢性给予氟哌啶醇（Hal）对健康大鼠固有免疫参数及相关系统的影响，并将其与 Hal 含量进行了比较。Hal 给药（0.5mg/kg，3 周）导致补体系统和止血的活性降低一倍。Hal 含量与补体的活性（r=−0.71）、腹腔巨噬细胞的吞噬活性（r=0.78）、白细胞弹性蛋白酶（r=−0.71）和谷胱甘肽-S-转移酶活性（r=−0.67）相关。Hal 完全阻断了 PMA 诱导的巨噬细胞中诱导型一氧化氮合酶的表达，并将其形态改变为“抗炎”表型。体内和体外数据的比较表明，Hal 对固有免疫的吞噬成分具有直接作用，对白细胞弹性蛋白酶和抗氧化酶具有间接作用。本研究的结果表明，Hal 显著影响体内平衡并引起多种复杂的生物学转化。
