Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2012;64(6):1368-80. doi: 10.1016/s1734-1140(12)70934-9.
Literature data show that administration of atypical antipsychotic drug, risperidone (RIS), enhances antidepressive action of fluoxetine (FLU). As antidepressive treatments also regulate immune functions, we examined whether combined administration of FLU and RIS to rats subsequently subjected to a forced swimming test (FST) modifies parameters of macrophage activity that are directly related to their immunomodulatory functions, i.e., arginase (ARG) activity and nitric oxide (NO) synthesis.
Antidepressive action of the drugs was assessed with FST. Peritoneal and pleural cells were eluted and selected parameters of immunoreactivity were assessed colorimetrically.
We found that the concomitant administration of FLU (10 mg/kg) and RIS (0.1 mg/kg) produced antidepressive-like effects in the FST,whereas the drugs were ineffective if administered separately. Stress related to the FST affected immune cell redistribution and changed some of the metabolic and immunomodulatory properties of macrophages. FLU administered to rats at a suboptimal dose for antidepressive action potently influenced macrophage immunomodulatory properties and redirected their activity toward anti-inflammatory M2 functional phenotype, as manifested by changes in the ARG/NO ratio. These effects resulted from a direct cellular influence of the drug, as well as its action via neuroendocrine pathways, as evidenced in peritoneal and pleural cells. Addition of RIS did not augment immunomodulatory action of FLU, though the combination showed antidepressant-like activity in the FST.
Our results suggest that when the drugs were administered together, FLU was potent enough to redirect macrophages toward M2 activity. It is also postulated that drug-induced changes in the immune system are not so closely related to antidepressant-like effects or might be secondary to those produced in the neuroendocrine system.
文献资料显示，非典型抗精神病药物利培酮（RIS）的给药增强了氟西汀（FLU）的抗抑郁作用。由于抗抑郁治疗也调节免疫功能，我们研究了在强迫游泳试验（FST）后给予 FLU 和 RIS 的联合给药是否会改变与免疫调节功能直接相关的巨噬细胞活性的参数，即精氨酸酶（ARG）活性和一氧化氮（NO）合成。
使用 FST 评估药物的抗抑郁作用。洗脱腹膜和胸膜细胞，并通过比色法评估免疫反应性的选择参数。
我们发现，FLU（10mg/kg）和 RIS（0.1mg/kg）的同时给药在 FST 中产生了抗抑郁样作用，而单独给药则无效。与 FST 相关的应激影响免疫细胞的重新分布，并改变了巨噬细胞的一些代谢和免疫调节特性。FLU 以低于抗抑郁作用的亚最佳剂量给药强烈影响巨噬细胞的免疫调节特性，并将其活性重定向为抗炎 M2 功能表型，表现为 ARG/NO 比值的变化。这些效应源自药物的直接细胞影响，以及其通过神经内分泌途径的作用，这在腹膜和胸膜细胞中得到了证明。尽管组合在 FST 中显示出抗抑郁样活性，但 RIS 并未增强 FLU 的免疫调节作用。
我们的结果表明，当药物一起给药时，FLU 足以将巨噬细胞重定向为 M2 活性。还假设药物诱导的免疫系统变化与抗抑郁样效应没有那么密切相关，或者可能是神经内分泌系统产生的变化的次要原因。
