Amlodipine inhibits the production of cytokines induced by ouabain

Recent studies have suggested that cytokines are capable of modifying cardiovascular function and that drugs used in the treatment of heart failure have various modulating properties on the production of cytokines, More recently, we have found that ouabain induces the production of cytokines, This study was performed to examine the effects of calcium channel blockers on the production of cytokines induced by a cardiac glycoside, Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers, PBMC were cultured in 0.1, 1, 10, and 30 mu mol/l amlodipine, diltiazem, and nifedipine in presence of 1 mu mol/l ouabain, After 24 h of incubation, IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were measured in the culture supernatants by enzyme-linked immunosorbent assay. Ouabain induced the production of IL-1 alpha, IL-1 beta and IL-6, but not of TNF-alpha. Induction of IL-1 beta was most prominent. The production of IL-1 alpha, and IL-6 was inhibited by amlodipine in a concentration-dependent manner and was significantly decreased at a concentration of 10 mu mol/l. IL-1 beta production was also inhibited by 30 mu mol/l amlodipine, In contrast, neither diltiazem nor nifedipine inhibited the production of these cytokines, The unique property of amlodipine to inhibit the production of IL-1 alpha, IL-1 beta and IL-6 may contribute to its beneficial effects in heart failure patients. (C) 2000 Academic Press.