PERIPHERAL-NERVE MYELIN MODULATES THE EFFECT OF ANTIDEPRESSANTS ON MAJOR HISTOCOMPATIBILITY COMPLEX EXPRESSION ON MACROPHAGES IN EXPERIMENTAL ALLERGIC NEURITIS

The effect of bovine peripheral nerve myelin (BPM) used for induction of experimental allergic neuritis (EAN) in Lewis rats, on antidepressa nts' modulation of interferon-gamma (IFN-gamma)-induced major histocom patibility complex (MHC) class I and II antigen expression on peritone al macrophages in EAN rats was studied. Antidepressants with different profiles concerning inhibition of the neuronal reuptake of the monoam ines serotonin (5-HT) and noradrenalin (NA), respectively, in concentr ations of 10(-4) to 10(-8) M were used. At the concentration of 1.0 U/ ml IFN-gamma, most antidepressants significantly enhanced both MHC cla ss I and class II expression, except maprotiline, a selective NA reupt ake inhibiting antidepressant that suppressed MHC class I expression. Zimeldine, a selective 5-HT reuptake inhibitor did not affect MHC clas s II expression. BPM in general had an enhancing effect on modulation of both MHC class I and class II expression by antidepressants. By its elf BPM enhanced MHC class I expression, but did not affect class II e xpression at IFN-gamma 1.0 U/ml. The modulating effect of BPM on regul ation of MHC expression by antidepressants could be the result of cont aminating T cells and release of IFN-gamma into cultures. The modulato ry effect of antidepressants on MHC expression may to some extent be e xerted by the action on 5-HT and/or NA regulation, but also by direct effects of antidepressants on macrophages. They probably play a role i n zimeldine-induced Guillain-Barre syndrome in some patients and in th e suppression of clinical signs of EAN in Lewis rats reported for some antidepressants.