EFFECTS OF METRONIDAZOLE AND ITS METABOLITES ON HISTAMINE IMMUNOSUPPRESSION ACTIVITY

We have previously reported that metronidazole treatment increases hum an lymphocyte proliferation showing individual differences. This drug and its metabolites are imidazole compounds like histamine and cimetid ine. The first is an endogenous amine that inhibits T-helper lymphocyt e proliferation, and the second is a histamine antagonist. We presentl y report the in vitro effects of histamine, cimetidine, imidazole, met ronidazole and its two principal metabolites (the acetic acid and hydr oxy forms), on the mitogenic response to phytohemagglutinin (PHA) stim ulation of human peripheral blood lymphocytes. Histamine decreased lym phocyte proliferation while (in order of potency) cimetidine, the hydr oxy metabolite of metronidazole, imidazole and metronidazole, increase d the mitogenic response to PHA in a dose-response fashion. The acetic acid metabolite lacked immunomodulatory effects. Competitive studies showed that cimetidine, metronidazole, and the hydroxy metabolite bloc ked the inhibitory effect of histamine on lymphocyte proliferation in a dose-related manner. This blockage was non-competitive, suggesting t hat the target of the imidazole compounds was not the active site of t he H-2 receptor.