Department of Pharmacology, Poznań University of Medical Sciences, Poznań, Poland.
Department of Pharmacology, Poznań University of Medical Sciences, Poznań, Poland.
Pharmacol Rep. 2014 Feb;66(1):22-7. doi: 10.1016/j.pharep.2013.06.003. Epub 2014 Feb 4.
Antidepressants are known to affect the immunological system through mechanisms which are not completely understood. The aim of the present study was to evaluate the effect of the atypical antidepressant mianserin on the levels of tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6) and interleukin-10 (IL-10) in the blood of rats in an experimental model of depression.
Male Wistar rats were subjected to chronic mild stress (CMS) according to Willner's method for 6 weeks. Following the development of anhedonia, the stressed and control rats (non-stressed animals) were treated with mianserin (10 mg/kg ip, twice daily) for three weeks. On the last day of the experiment, a lipopolysaccharide (LPS, 100 μg/kg ip) was injected to mianserin- or vehicle-treated rats. TNFα, IL-6 and IL-10 levels in the blood of the rats were assayed using ELISA methods.
The results indicated a significantly increased TNFα level in stressed animals when compared with the non-stressed (control) group. The levels of IL-6 and IL-10 were also elevated, especially after LPS administration. Treatment with mianserin resulted in a significant lowering of TNFα and IL-6 levels both in LPS-treated and LPS-untreated animals. There was also a decrease in IL-10 concentration in LPS-treated stressed animals.
The results confirm an increase in proinflammatory cytokines in the blood of rats with experimentally induced depression and show the protective role of the activity of mianserin on the cytokine levels, expressed in a lowering of TNFα and IL-6 levels in stressed animals, and of IL-10 levels after LPS administration.
已知抗抑郁药通过尚未完全了解的机制影响免疫系统。本研究旨在评估非典型抗抑郁药米氮平对抑郁实验模型大鼠血液中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）水平的影响。
雄性 Wistar 大鼠按照 Willner 的方法进行 6 周慢性轻度应激（CMS）。在快感缺乏症发展后，应激和对照大鼠（非应激动物）用米氮平（10mg/kg，ip，每日两次）治疗 3 周。在实验的最后一天，给米氮平或载体处理的大鼠注射脂多糖（LPS，100μg/kg，ip）。使用 ELISA 方法检测大鼠血液中的 TNF-α、IL-6 和 IL-10 水平。
结果表明，与非应激（对照）组相比，应激动物的 TNF-α水平显著升高。IL-6 和 IL-10 的水平也升高，尤其是在 LPS 给药后。米氮平治疗导致 LPS 处理和未处理的应激动物的 TNF-α和 IL-6 水平显著降低。LPS 处理的应激动物的 IL-10 浓度也降低。
这些结果证实了实验性诱导的抑郁大鼠血液中促炎细胞因子的增加，并显示了米氮平活性对细胞因子水平的保护作用，表现为应激动物 TNF-α和 IL-6 水平降低，以及 LPS 给药后 IL-10 水平降低。
