CALCITRIOL EFFECT ON NATURAL-KILLER-CELLS FROM HEMODIALYZED AND NORMAL SUBJECTS

Patients with chronic renal failure have a decreased secretion of calc itriol (CTR). They also show an impaired cellular immune response incl uding a defective natural killer (NK) cell-mediated activity. The aim of this study was to analyze, in vivo and in vitro, the effect of CTR on NK cell cytotoxicity in healthy control subjects and in hemodialyze d (HD) patients. Our results show that HD patients had baseline-depres sed NK cell activity when compared with controls (P < 0.001), which in creased significantly after 1 month of oral CTR treatment (0.5 mu g/da y) (P < 0.001). Calcitriol treatment also induced a significant increa se in CTR serum levels (P < 0.001) and a significant decrease (P < 0.0 01) in total parathyroid hormone (PTH). In vitro CTR treatment (10(-7) M) of peripheral blood mononuclear cells (PBMC) increased NK cell-med iated cytotoxicity after 24 hours of incubation with a maximum at 48 h ours (P < 0.001). In vitro CTR treatment at doses of 10(-11) and 10(-9 ) M did not significantly increase NK cytotoxic activity. The enhanced NK activity after CTR treatment was not the consequence of increased numbers of CD56 positive cells, nor to lymphocyte activation, as teste d by the expression of the interleukin 2 receptor p55 alpha chain (CD2 5) on their surface. In vitro treatment of PBMC from HD patients with CTR (10(-7) M, during 48 hours) also induced a strong increase in NK c ell cytotoxicity (P < 0.001). These results demonstrate a positive rol e of CTR in the stimulation of NK cell activity and support the hypoth esis of a direct steroid-mediated action of CTR on NK cells, although an indirect effect mediated by the CTR-induced PTH decrease in vivo ca nnot be excluded. Our data also raise the possibility for potential th erapeutic uses of this hormone in immunomodulation of patients with de pressed NK cell activity.