EFFECT OF MONOAMINE REUPTAKE INHIBITING ANTIDEPRESSANTS ON MAJOR HISTOCOMPATIBILITY COMPLEX EXPRESSION ON MACROPHAGES IN NORMAL RATS AND RATS WITH EXPERIMENTAL ALLERGIC NEURITIS (EAN)

This study examined the modulation of IFN-gamma induced MHC class I an d II expression on normal Lewis rats and rats with EAN peritoneal macr ophages cultured in the absence or presence of 10(-4)-10(-8) M of the 5-HT reuptake inhibiting antidepressants zimeldine, and its metabolite s norzimeldine and cpp200 oxalate as well as the antidepressants clomi pramine and imipramine, in addition amitriptyline, nortriptyline and m aprotiline in EAN rats. In normal rats, MHC class I expression was sup pressed by the antidepressants zimeldine, norzimeldine and cpp200 oxal ate at concentrations up to 10(-5) M. At concentrations between 10(-6) to 10(-8) M, the same drugs significantly enhanced MHC class expressi on. Clomipramine at 10(-8) M and imipramine at 10(-6)-10(-7) M enhance d MHC class I expression, while the MHC class II expression was not si gnificantly influenced by concentrations less than or equal to 10(-5) M of these two drugs. In EAN rats, MHC class I expression was enhanced by zimeldine, cpp200, imipramine, and nortriptyline at 10(-5)-10(-8) M, amitriptyline at 10(-5)-10(-7) M as well as by norzimeldine and clo mipramine at 10(-6) M-10(-8) M. However, maprotiline at 10(-4) 10(-6) M suppressed class I expression in the presence of 0.5 U/ml and 1.0 U/ ml of IFN-gamma. MHC class II expression was suppressed by cpp200 and clomipramine at 10(-4)-10(-5) M in presence of 0.5 U/ml of IFN-gamma, At concentrations < 10(-5) M most tested drugs significantly enhanced IFN-gamma induced MHC class II expression. Compared to the results in normal rats, drug effects on EAN macrophages were more pronounced and reached higher levels of significance. The 5-HT reuptake inhibiting an tidepressants also exerted a modulatory effect on MHC class I and II i n EAN rat macrophages even in the absence of IFN-gamma. The modulatory effect of antidepressant drugs on IFN-gamma induced MHC class I and I I expression may contribute to their influence on demyelinating autoim mune diseases, and may have implications for their clinical use.