Amiodarone inhibits production of tumor necrosis factor-alpha by human mononuclear cells: a possible mechanism for its effect in heart failure.

BACKGROUND

Recent studies suggest that cytokines such as tumor necrosis 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 drug shown to be beneficial in some patients suffering from heart failure) versus other antiarrhythmic agents on the production of cytokines in vitro.

RESULTS

Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers. PBMC were cultured with 0.1, 1, and 10 micromol/L of amiodarone, quinidine, disopyramide, and lidocaine in the presence of lipopolysaccharide. After 24 hours' incubation, TNF-alpha, IL-1beta, and IL-6 were measured in the culture supernatants by an enzyme-linked immunosorbent assay. TNF-alpha production was inhibited by amiodarone but stimulated by quinidine in a concentration-dependent manner. Disopyramide and lidocaine tended to increase TNF-alpha production. IL-6 production was decreased by amiodarone in all concentrations but was increased significantly by disopyramide. Modulation of IL-1beta production by amiodarone was biphasic and significantly increased at a concentration of 10 micromol/L.

CONCLUSIONS

These previously unrecognized immunomodulatory effects of amiodarone may contribute to its beneficial effects in heart failure patients.