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双氯芬酸和抗抑郁药对星形胶质细胞培养中炎症反应的影响。

Effect of diclofenac and antidepressants on the inflammatory response in astrocyte cell culture.

作者信息

Al-Amin Md Mamun, Uddin Mir Muhammad Nasir, Rahman Md Mahbubur, Reza Hasan Mahmud, Rana Md Sohel

机构信息

Department of Pharmacy, North South University, Plot-15, Block-B, Bashundhara, Dhaka, 1229, Bangladesh,

出版信息

Inflammopharmacology. 2013 Dec;21(6):421-5. doi: 10.1007/s10787-013-0181-9. Epub 2013 Jul 30.

DOI:10.1007/s10787-013-0181-9
PMID:23896940
Abstract

Central nervous system (CNS) has a completely separate immune system that communicates with the neurons by small molecules called cytokines. Cytokines are involved in many crucial processes in neuron including cell metabolism and neurotransmitter synthesis. It has been reported that cytokine imbalance is involved in the progression of many CNS diseases such as neuropsychiatric disorders (depression, schizophrenia, autism, and bipolar disorder) and neurodegenerative disorders (Parkinson's and Alzheimer's disease). Here, the effects of diclofenac, different antidepressants (sertraline, venlafaxine, and fluvoxamine), and vitamin B₆ (pyridoxine) on IL-10 and tumor necrosis factor-α (TNF-α) change with and without immune challenges with lipopolysaccharide (LPS) were investigated in in vitro culture of astrocytes from 2-day-old Swiss-Albino mice. Diclofenac and Sertraline significantly (p < 0.05) improves anti-inflammatory cytokine (IL-10) while suppress (p < 0.05) LPS-induced elevated level of pro-inflammatory mediators (TNF-α) in astrocyte culture. Pyridoxine was not able to reduce (p > 0.05) TNF-α in the astrocyte culture. Antidepressant (sertraline) showed positive effects (increased IL-10 and reduced TNF-α level) possibly through the suppression of Th1 lymphocytes and monocytes and stimulation of Th2 lymphocytes and monocytes/macrophages. NSAID (diclofenac) showed positive immune regulation effect possibly through the inhibition of cyclo-oxygenase enzyme. Based on these findings, it may conclude that, diclofenac and antidepressants (sertraline) may positively contribute in the cytokine production in astrocyte cell culture.

摘要

中枢神经系统(CNS)有一个完全独立的免疫系统,该系统通过称为细胞因子的小分子与神经元进行通信。细胞因子参与神经元的许多关键过程,包括细胞代谢和神经递质合成。据报道,细胞因子失衡与许多中枢神经系统疾病的进展有关,如神经精神疾病(抑郁症、精神分裂症、自闭症和双相情感障碍)和神经退行性疾病(帕金森病和阿尔茨海默病)。在此,研究了双氯芬酸、不同的抗抑郁药(舍曲林、文拉法辛和氟伏沙明)以及维生素B₆(吡哆醇)在有或无脂多糖(LPS)免疫刺激的情况下,对来自2日龄瑞士白化小鼠星形胶质细胞体外培养中白细胞介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)变化的影响。双氯芬酸和舍曲林显著(p<0.05)提高抗炎细胞因子(IL-10),同时抑制(p<0.05)LPS诱导的星形胶质细胞培养中促炎介质(TNF-α)水平的升高。吡哆醇未能降低(p>0.05)星形胶质细胞培养中的TNF-α。抗抑郁药(舍曲林)可能通过抑制Th1淋巴细胞和单核细胞以及刺激Th2淋巴细胞和单核细胞/巨噬细胞而显示出积极作用(IL-10增加,TNF-α水平降低)。非甾体抗炎药(双氯芬酸)可能通过抑制环氧化酶显示出积极的免疫调节作用。基于这些发现,可以得出结论,双氯芬酸和抗抑郁药(舍曲林)可能对星形胶质细胞培养中的细胞因子产生有积极贡献。

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