VITAMIN-D THERAPY MODULATES CYTOKINE SECRETION IN PATIENTS WITH RENAL-FAILURE

In studies in vitro calcitriol (1,25-dihydroxyvitamin D3) inhibits lym phocyte proliferation and modulates several monocyte functions, includ ing the secretion of prostaglandins and monokines. However its effects on monokine production in vivo are not known. Therefore we studied th e secretion of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF ) by peripheral blood mononuclear cells (PBMC) from 7 patients on peri odic hemodialysis, before and after oral treatment with calcitriol (0. 5 mug daily) for 1 month. Calcitriol therapy resulted in significant i ncreases in the phorbol myristate acetate (PMA)-induced secretion of I L-1 and IL-6 (p = 0.04 and 0.03, respectively). This was a transient e ffect, observable by day 7 of therapy, but no longer evident by day 30 . However, calcitriol induced a progressive reduction of TNF secretion (down to 53% of control values by day 30, p = 0.02). There were no co rrelations between the individual changes in calcium/PTH and cytokine release. These results show that doses of calcitriol within the therap eutic range induce marked changes in cytokine secretion by PBMC from u remic patients.