Clomipramine and imipramine suppress clinical signs and T and B cell response to myelin proteins in experimental autoimmune neuritis in Lewis rats.
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.
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Jie.Zhu@cnsf.ki.se
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Bengtsson
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Ekerling
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Thorell
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Olsson
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D018759:Adrenergic Uptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002417:Cattle; D002997:Clomipramine / Q000097:blood / Q000494:pharmacology*; D007099:Imipramine / Q000097:blood / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D009185:Myelin Proteins / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D002997:Clomipramine; D007099:Imipramine; D007074:Immunoglobulin G; D007371:Interferon-gamma; D009185:Myelin Proteins; D017367:Selective Serotonin Reuptake Inhibitors