Peripheral Nerve Myelin Modulates the Effect of Antidepressants on Major Histocompatibility Complex Expression on Macrophages in Experimental Allergic Neuritis

Abstract

The effect of bovine peripheral nerve myelin (BPM) used for induction of experimental allergic neuritis (EAN) in Lewis rats, on antidepressants' modulation of interferon-gamma (IFN-γ)-induced major histocompatibility complex (MHC) class I and II antigen expression on peritoneal macrophages in EAN rats was studied. Antidepressants with different profiles concerning inhibition of the neuronal reuptake of the monoamines serotonin (5-HT) and noradrenalin (NA), respectively, in concentrations of 10⁻⁴ to 10⁻⁸ M were used. At the concentration of 1.0 U/ml IFN-γ, most antidepressants significantly enhanced both MHC class I and class II expression, except maprotiline, a selective NA reuptake inhibiting antidepressant that suppressed MHC class I expression. Zimeldine, a selective 5-HT reuptake inhibitor did not affect MHC class II expression. BPM in general had an enhancing effect on modulation of both MHC class I and class II expression by antidepressants. By itself BPM enhanced MHC class I expression, but did not affect class II expression at IFN-γ 1.0 U/ml. The modulating effect of BPM on regulation of MHC expression by antidepressants could be the result of contaminating T cells and release of IFN-γ into cultures. The modulatory effect of antidepressants on MHC expression may to some extent be exerted by the action on 5-HT and/or NA regulation, but also by direct effects of antidepressants on macrophages. They probably play a role in zimeldine-induced Guillain-Barré syndrome in some patients and in the suppression of clinical signs of EAN in Lewis rats reported for some antidepressants.