Effect of tacrolimus and cyclosporine A on suppression of albumin secretion induced by inflammatory cytokines in cultured human hepatocytes

Abstract

To investigate the effect of tacrolimus (FK506) and cyclosporine A (CSA) on albumin secretion and on the IL-6 -induced suppression of albumin synthesis in cultured human hepatocytes. HepG2 cells were cultured separately with IL-6, IL-10 (0-10 ng/ml) and FK506, CSA (0-100 ng/ml) for 48 h. In another experiment, HepG2 cells were incubated with different amounts of FK506 and CSA (0-10 ng/ml) in the presence of IL-6 (5 ng/ml). The albumin levels in these groups of hepatic cultures were measured by radioimmunoassay. The concentration of LDH secreted by cells stimulated with FK506 and CSA was detected by spectrophotometry. IL-6 decreased the levels of albumin in a dose-dependent manner (P < 0.01), maximal inhibition was observed at 5 ng/ml. Neither IL-10 nor FK506 modulated albumin production. However, FK506 decreased LDH levels in the supernatant of cells (P < 0.05) and prevented the IL-6-induced suppression of albumin synthesis (P < 0.01) in a dose dependent manner. In contrast, CSA caused only a slight decrease in albumin levels (P < 0.05). In addition, CSA slightly increased the amount of LDH in HepG2 cells and did not interfere with the IL-6-induced decrease in albumin synthesis. These findings suggest that IL-6, but not IL- 10, may play an important role in the suppression of hepatic albumin secretion. FK506 but not CSA protects against the suppression of hepatic albumin synthesis caused by IL-6.