A synthetic analogue of vitamin D3, 22-oxa-1 alpha,25-dihydroxyvitamin D3, is a potent modulator of in vivo immunoregulating activity without inducing hypercalcemia in mice.
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 greater than 1 alpha,25(OH)2D3 not equal to 20-oxa-1 alpha,25(OH)2D3 not equal to 22-oxa-1 alpha(OH)D3 greater than 1 alpha(OH)D3 not equal to 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.
Abe
J
J
Research Laboratories, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Takita
Y
Y
Nakano
T
T
Miyaura
C
C
Suda
T
T
Nishii
Y
Y
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000502:physiology; D002118:Calcium / Q000097:blood*; D002762:Cholecalciferol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000494:pharmacology; D005260:Female; D006934:Hypercalcemia / Q000139:chemically induced; D007107:Immune System / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C
D004872:Ergocalciferols; D002762:Cholecalciferol; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium