CLOMIPRAMINE AND IMIPRAMINE SUPPRESS CLINICAL SIGNS AND T-CELL AND B-CELL RESPONSE TO MYELIN PROTEINS IN EXPERIMENTAL AUTOIMMUNE NEURITIS IN LEWIS

5-Hydroxytryptamine (5-HT) reuptake inhibitors of the zimeldine-type h ave induced polyneuropathies similar to Guillain-Barre syndrome (GBS) in patients with endogenous depression. Some monoamine neurotransmitte rs have been shown to affect immune reactions in vivo and in vitro in a concentration-dependent manner. We therefore studied the effect of t he monoamine reuptake inhibitory anti-depressants, clomipramine and im ipramine on specific immune response and the clinical course of experi mental autoimmune neuritis (EAN), the animal model of GBS in humans. C lomipramine and imipramine both suppressed clinical signs of EAN induc ed by immunization with bovine peripheral nerve myelin (BPM), when giv en at a dose of 20 mg/kg/day intraperitoneally, via osmotic pumps. Clo mipramine and imipramine reduced the numbers of Th1 cells secreting IF N-gamma in response to the neuritogenic myelin proteins BPM, P0 and P2 among lymph node mononuclear cells (MNC) from rats with EAN. The leve ls of cells secreting IgG antibodies to BPM, P2 and GM1 in lymph nodes were reduced at the height of EAN in clomipramine and imipramine trea ted animals. The action of clomipramine and imipramine on induced IFN- gamma and anti-myelin antibodies suggests that the mechanism for the s uppressive effect of those substances on EAN symptoms may be due to an action on myelin T and B cell autoreactivity. Considering that the ma in common pharmacological principle of clomipramine and imipramine is to increase the functional activity of the noradrenaline (NA) and sero tonin (5-HT) of the monoamines, it seems justified to postulate that t he actions of clomipramine and imipramine demonstrated in this study t o 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 auto immune diseases, and for further studies of immunological mechanisms i n the pathogenesis of depressive disorders. (C) 1998 Academic Press.