Paricalcitol reduces basal and lipopolysaccharide-induced (LPS) TNF-alpha and IL-8 production by human peripheral blood mononuclear cells.

INTRODUCTION: Vitamin D and its analogues proved to exert immunomodulatory effects. Paricalcitol is a vitamin D analogue that is safe. It has been used for years in the treatment of secondary hyperparathyroidism in hemodialysis patients and, importantly, it is less calcemic than vitamin D. In this study the immunomodulatory/anti-inflammatory properties of paricalcitol were evaluated in vitro. SUBJECT AND METHODS: Ten healthy volunteers enrolled into the study. Peripheral blood mononuclear cells (PBMC) at a concentration of 10(6) cells per well were cultured for 48 h in the presence or not of lipopolysaccharide (LPS) (100 ng/ml) and in the presence or not of paricalcitol (10(-8) M). TNF-alpha and IL-8 were measured in the supernatants by ELISA.
RESULTS: Basal TNF-alpha concentration (50.3 +/- 22 pg/ml) was reduced by paricalcitol (44.1 +/- 23.2 pg/ml). LPS increased TNF-alpha concentration (150.0 +/- 81.7 pg/ml), but paricalcitol reduced it (121.1 +/- 69.0 pg/ml). The effect of paricalcitol on IL-8 production was more profound. Basal IL-8 concentration (1926 +/- 455 pg/ml) was reduced by paricalcitol (1273 +/- 472 pg/ml). LPS increased IL-8 concentration (2361 +/- 385 pg/ml), but paricalcitol returned it to its basal level (1849 +/- 417 pg/ml).
CONCLUSION: The in vitro inhibition of transforming growth factor alpha and interleukin 8 by paricalcitol confirms the immunomodulatory properties of this vitamin D analogue.