The effect of vitamin D analogs and of vitamin D-binding protein on lymphocyte proliferation

Abstract

In the absence of vitamin D-binding protein (DBP), 1,25-(OH) 2D 3 10 −12M significantly inhibited the [ 3H]thymidine incorporation in human lymphocytes during mixed lymphocyte cultures (MLC) or after phyto-hemaglutinin (PHA) stimulation. In the presence of a physiological concentration of DBP (5 × 10 −6M), the concentration of 1,25-(OH) 2D 3 required for inhibition was 10 −12 M (for PHA-cultures) and 10 −9 M (for MLC). Several vitamin D analogs were compared for their inhibitory action on PHA stimulation. In the absence of DBP, the concentration necessary for 50% inhibition of [su3H]thymidine incorporation ranged from 10 −12M [1,25-(OH) 2D 3 and 24,24-F 2-1,25-(OH) 2D 3], over 10 −10M [1,24R, 25-(OH) 3D 3; 1,25S, 26-(OH) 3D 3 and 26,27-F 6-1,25-(OH) 2D 3] and 10 −8M [25 OHD 3 and 24,25-(OH) 2D3] to 10 −6M [calcitriol-lactone]. This rank order correlates with the binding affinity of the various analogs to the cytoplasmic l,25-(OH) 2D 3-receptor. DBP counteracted the inhibitory effect of all analogs and the degree of counteraction was directly proportional to the binding affinity between DBP and the vitamin D analog. DBP thus decreased the in vitro inhibitory action of 1,25-(OH) 2D 3 and its analogs on lymphocyte proliferation. Of all analogs tested, only 1,25-(OH) 2D 3 had a significant effect at a physiological concentration.