A SYNTHETIC ANALOGUE OF VITAMIN D3, 22-OXA-lα,25-DIHYDROXYVITAMIN D3IS A POTENT MODULATOR OF IN VIVO IMMUNOREGULATING ACTIVITY WITHOUT INDUCING HYPERCALCEMIA IN MICE

Abstract

The in vivo immunoregulating activity and the hypercalcemic action of 4 synthetic analogues of vitamin D3 with an oxygen atom in the side chain were compared with those of 1.alpha.,25-dihydroxyvitamin D3 (1.alpha.,25(OH)2D3] in mice. Oral administration of these vitamin D3 compounds augmented the primary immune response, induced by immunization with a suboptimal number of sheep erythrocytes, without inducing hypercalcemia. The order of the in vivo potency to induce the immune response was 22-oxa-1.alpha.,25(OH)2D3 > 1.alpha.,25(OH)2D3 .apprxeq. 20-oxa-1.alpha.,25(OH)2D3 .apprxeq. 22-oxa-1.alpha.(OH)D3 .apprxeq. 20-oxa-1.alpha.(OH)D3. 22-Oxa-1.alpha.,25(OH)2D3 was about 50 times more potent than 1.alpha.,25(OH)2D3 in inducing the in vivo primary immune response, but the former was only 1/100 as active as the latter in inducing hypercalcemia. These results suggest that the immunoregulating activity of vitamin D compounds can be separated structurally from their hypercalcemic action in vivo.