Dredge K, Connor T J, Kelly J P, Leonard B E
Department of Pharmacology, National University of Ireland, Galway, Ireland
Int J Immunopharmacol. 1999 Oct;21(10):663-73. doi: 10.1016/s0192-0561(99)00042-9.
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 microg/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)-1beta 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-1beta 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 of 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.
三环类抗抑郁药（TCAs）中的丙咪嗪是其中一种，常用于治疗抑郁症和其他形式的精神疾病。关于TCAs对免疫功能的抑制作用已有许多报道。然而，关于TCAs对免疫系统的影响，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接触此类药物，或药物给药后免疫的体外测量。因此，在本研究中，使用细菌脂多糖（LPS）（100微克/千克；腹腔注射）进行体内刺激，以评估单次高剂量给予TCAs丙咪嗪（100毫克/千克，口服）后的免疫能力。结果表明，丙咪嗪预处理在给药后3小时和6小时均抑制LPS诱导的促炎细胞因子肿瘤坏死因子（TNF）-α血清浓度升高。然而，在任何一个检测时间点，丙咪嗪治疗后LPS诱导的白细胞介素（IL）-1β分泌均未显著改变。此外，还测量了皮质酮和抗炎细胞因子IL-10的血清浓度，丙咪嗪治疗未能改变这些免疫抑制剂的基础水平或LPS诱导的升高。总之，虽然IL-1β和TNF-α都是巨噬细胞衍生的促炎细胞因子，但本研究表明这些细胞因子对TCAs丙咪嗪的抑制作用具有不同的敏感性。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升高或抗炎细胞因子IL-10分泌的增加。讨论了这些发现与抗抑郁药诱导的免疫毒性的相关性。
