Inhibition of human natural killer cell and lymphokine-activated killer cell cytotoxicity and differentiation by vitamin D3.

Recent data suggest that vitamin D3 may be capable of immunoregulation after it is converted to an active metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The effect of vitamin D3 and 1,25(OH)2D3 on human natural killer (NK) cells and their activation by interferon (IFN) and interleukin 2 (IL-2) was investigated. Vitamin D3 and 1,25(OH)2D3 inhibited NK cytotoxicity in a dose-dependent manner. Pretreatment of non-adherent (NA) cells at 37 degrees C for 18 h with the vitamins also led to inhibition of NK activity. Both the inhibition of NK lysis and pretreatment of NA cells were dependent on the concentrations of fetal calf serum (FCS) in the medium. The inhibition of NK activity was less effective in the presence of 10% FCS than with 1% FCS. Vitamin D3 inhibited both IFN and IL-2 activation of NK activity. However, increasing doses of IL-2 were able to abrogate the inhibition caused by vitamin D3. Vitamin D3 was able to inhibit NK activity of phytohaemagglutinin and IL-2-activated cells, and also inhibit the proliferation and lymphokine-activated killer activity induced by IL-2. NA cells pretreated with vitamin D3 did not respond well to IL-2. NA cells pretreated with low doses of IL-2 were sensitive to inhibition by vitamin D3 while those pretreated with high doses of IL-2 were not. The data presented suggest that vitamin D3 and 1,25(OH)2D3 inhibit NK activity and LAK cellular differentiation.