Zhu J, Bengtsson B O, Mix E, Ekerling L, Thorell L H, Olsson T, Link H
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
J Autoimmun. 1998 Aug;11(4):319-27. doi: 10.1006/jaut.1998.0209.
5-Hydroxytryptamine (5-HT) reuptake inhibitors of the zimeldine-type have induced polyneuropathies similar to Guillain-Barré syndrome (GBS) in patients with endogenous depression. Some monoamine neurotransmitters have been shown to affect immune reactions in vivo and in vitro in a concentration-dependent manner. We therefore studied the effect of the monoamine reuptake inhibitory anti-depressants, clomipramine and imipramine on specific immune response and the clinical course of experimental autoimmune neuritis (EAN), the animal model of GBS in humans. Clomipramine and imipramine both suppressed clinical signs of EAN induced by immunization with bovine peripheral nerve myelin (BPM), when given at a dose of 20 mg/kg/day intraperitoneally, via osmotic pumps. Clomipramine and imipramine reduced the numbers of Th1 cells secreting IFN-gamma in response to the neuritogenic myelin proteins BPM, P0 and P2 among lymph node mononuclear cells (MNC) from rats with EAN. The levels of cells secreting IgG antibodies to BPM, P2 and GM1 in lymph nodes were reduced at the height of EAN in clomipramine and imipramine treated animals. The action of clomipramine and imipramine on induced IFN-gamma and anti-myelin antibodies suggests that the mechanism for the suppressive effect of those substances on EAN symptoms may be due to an action on myelin T and B cell autoreactivity. Considering that the main common pharmacological principle of clomipramine and imipramine is to increase the functional activity of the nor-adrenaline (NA) and serotonin (5-HT) of the monoamines, it seems justified to postulate that the actions of clomipramine and imipramine demonstrated in this study to some extent involve NA and/or 5-HT. The immunomodulatory effects of clomipramine and imipramine call for further research on the potential role of drugs acting on the monoamine system in the treatment of autoimmune diseases, and for further studies of immunological mechanisms in the pathogenesis of depressive disorders.
齐美利定类型的5-羟色胺（5-HT）再摄取抑制剂在患有内源性抑郁症的患者中诱发了类似于格林-巴利综合征（GBS）的多发性神经病。一些单胺神经递质已被证明在体内和体外以浓度依赖的方式影响免疫反应。因此，我们研究了单胺再摄取抑制性抗抑郁药氯米帕明和丙咪嗪对特异性免疫反应以及实验性自身免疫性神经炎（EAN）临床病程的影响，EAN是人类GBS的动物模型。当通过渗透泵以20mg/kg/天的剂量腹腔注射时，氯米帕明和丙咪嗪均抑制了用牛周围神经髓磷脂（BPM）免疫诱导的EAN的临床症状。氯米帕明和丙咪嗪减少了EAN大鼠淋巴结单核细胞（MNC）中因致神经炎髓磷脂蛋白BPM、P0和P2而分泌γ干扰素的Th1细胞数量。在氯米帕明和丙咪嗪治疗的动物中，EAN高峰期淋巴结中分泌针对BPM、P2和GM1的IgG抗体的细胞水平降低。氯米帕明和丙咪嗪对诱导的γ干扰素和抗髓磷脂抗体的作用表明，这些物质对EAN症状的抑制作用机制可能是由于对髓磷脂T和B细胞自身反应性的作用。考虑到氯米帕明和丙咪嗪的主要共同药理原理是增加单胺中去甲肾上腺素（NA）和5-羟色胺（5-HT）的功能活性，推测本研究中氯米帕明和丙咪嗪的作用在一定程度上涉及NA和/或5-HT似乎是合理的。氯米帕明和丙咪嗪的免疫调节作用需要进一步研究作用于单胺系统的药物在自身免疫性疾病治疗中的潜在作用，以及进一步研究抑郁症发病机制中的免疫机制。
