AMIODARONE INHIBITS PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA BY HUMAN MONONUCLEAR-CELLS

Background Recent studies suggest that cytokines such as tumor necrosi s factor (TNF)-alpha and interleukins (ILs) are capable of modulating cardiovascular function and that drugs used in the treatment of heart failure have various modulatory effects on the production of cytokines . This study was performed to examine the effects of amiodarone (a dru g shown to be beneficial in some patients suffering from heart failure ) versus other antiarrhythmic agents on the production of cytokines in vitro. Methods and Results Human peripheral blood mononuclear cells ( PBMC) were obtained from healthy volunteers. PBMC were cultured with 0 .1, 1, and 10 mu mol/L of amiodarone, quinidine, disopyramide, and lid ocaine in the presence of lipopolysaccharide. After 24 hours' incubati on, TNF-alpha, IL-1 beta, and IL-6 were measured in the culture supern atants bf an enzyme-linked immunosorbent assay. TNF-alpha production w as inhibited by amiodarone but stimulated by quinidine in a concentrat ion-dependent manner. Disopyramide and lidocaine tended to increase TN F-alpha production. IL-6 production was decreased by amiodarone in all concentrations but was increased significantly by disopyramide. Modul ation of IL-1 beta production by amiodarone was biphasic and significa ntly increased st a concentration of 10 mu mol/L. Conclusions These pr eviously unrecognized immunomodulatory effects of amiodarone may contr ibute to its beneficial effects in heart failure patients.