Differential effect of a single high dose of the tricyclic antidepressant imipramine on interleukin-1β and tumor necrosis factor-α secretion following an in vivo lipopolysaccharide challenge in rats
Differential effect of a single high dose of the tricyclic antidepressant imipramine on interleukin-1β and tumor necrosis factor-α secretion following an in vivo lipopolysaccharide challenge in rats
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DOI：
10.1016/s0192-0561(99)00042-9
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发表时间：
1999-10-01
期刊：
影响因子：
--
通讯作者：
Leonard, BE
中科院分区：
文献类型：
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作者：
Dredge, K;Connor, TJ;Leonard, BE
三环类抗抑郁药（TCA），丙咪嗪是其中之一，常用于治疗抑郁症和其他形式的精神疾病。关于TCA对免疫功能的抑制作用已有许多报道。然而，关于TCA对免疫系统的影响的信息仍然有限，因为迄今为止进行的许多研究都集中在体外暴露于此类药物或给药后的免疫力的离体测量上。因此，在本研究中，用细菌脂多糖（LPS）（100 μ g/kg; i. p.）用于评估单次高剂量TCA丙咪嗪（100 mg/kg，p.o.）给药后的免疫活性。结果表明，丙咪嗪预处理抑制LPS诱导的促炎性细胞因子，肿瘤坏死因子（TNF）-α的血清浓度增加3和6小时，给药后。然而，LPS诱导的白细胞介素（IL）-1 β分泌没有显着改变丙咪嗪治疗后，在任何时间点检查。此外，血清皮质酮和IL-10的血清浓度进行了测量，丙咪嗪治疗未能改变任何基础，或LPS诱导的这些免疫抑制剂的增加。总之，虽然IL-1 β和TNF-α都是巨噬细胞衍生的促炎细胞因子，本研究表明这些细胞因子对TCA丙咪嗪的抑制作用的敏感性不同。此外，丙咪嗪对LPS诱导的TNF-α分泌的抑制作用不能归因于糖皮质激素水平的增加，或TNF-α细胞因子IL-10分泌的增加。这些研究结果的相关性抗抑郁药诱导的免疫毒性进行了讨论。(C)1999年国际免疫药理学学会。由Elsevier Science Ltd.出版，版权所有。
Tricyclic antidepressants (TCAs) of which imipramine is one, are commonly used in the treatment of depressive disorders and other forms of psychiatric illness. There have been many reports regarding the suppressive effects of TCAs on immune function. However, information is still limited regarding the effects of TCAs on the immune system, as many of the studies conducted to date have concentrated on in vitro exposure to such drugs, or ex vivo measures of immunity following drug administration. Thus in the present investigation, an in vivo challenge with bacterial lipopolysaccharide (LPS) (100 mu g/kg; i.p.) was used to assess immunocompetence following administration of a single high dose of the TCA, imipramine (100 mg/kg, p.o.). The results demonstrated that imipramine pretreatment inhibits LPS-induced increases in serum concentrations of the proinflammatory cytokine, tumor necrosis factor (TNF)-alpha both 3 and 6 h, following administration. However, LPS-induced interleukin (IL)-1 beta secretion was not significantly altered following imipramine treatment at either of the timepoints examined. In addition, serum concentrations of corticosterone and the antiinflammatory cytokine IL-10 were measured, and imipramine treatment failed to alter either basal, or LPS-induced increases in these immunosuppressive agents. In conclusion, although IL-1 beta and TNF-alpha are both macrophage-derived proinflammatory cytokines, the present study demonstrates a differential sensitivity of these cytokines to the suppressive effects of the TCA imipramine. Furthermore, the suppressive effects df imipramine on LPS-induced TNF-alpha secretion could not be attributed to either increased glucocorticoid levels, or increased secretion of the antiinflammatory cytokine IL-10. The relevance of these findings to antidepressant-induced immunotoxicity are discussed. (C) 1999 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.