Amlodipine inhibits the production of cytokines induced by ouabain

Recent studies have suggested that cytokines are capable of modifying cardi ovascular function and that drugs used in the treatment of heart failure ha ve various modulating properties on the production of cytokines, More recen tly, we have found that ouabain induces the production of cytokines, This s tudy was performed to examine the effects of calcium channel blockers on th e 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 nif edipine in presence of 1 mu mol/l ouabain, After 24 h of incubation, IL-1 a lpha, IL-1 beta, IL-6, and TNF-alpha were measured in the culture supernata nts 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 be ta was most prominent. The production of IL-1 alpha, and IL-6 was inhibited by amlodipine in a concentration-dependent manner and was significantly de creased at a concentration of 10 mu mol/l. IL-1 beta production was also in hibited by 30 mu mol/l amlodipine, In contrast, neither diltiazem nor nifed ipine inhibited the production of these cytokines, The unique property of a mlodipine to inhibit the production of IL-1 alpha, IL-1 beta and IL-6 may c ontribute to its beneficial effects in heart failure patients. (C) 2000 Aca demic Press.