Abe J, Takita Y, Nakano T, Miyaura C, Suda T, Nishii Y
Research Laboratories, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
Endocrinology. 1989 May;124(5):2645-7. doi: 10.1210/endo-124-5-2645.
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.
将4种侧链含有氧原子的维生素D3合成类似物的体内免疫调节活性和高钙血症作用，与1α,25 - 二羟基维生素D3[1α,25(OH)2D3]在小鼠体内的情况进行了比较。口服这些维生素D3化合物可增强由次优数量的绵羊红细胞免疫诱导的初次免疫反应，且不会引发高钙血症。诱导免疫反应的体内效力顺序为：22 - 氧杂 - 1α,25(OH)2D3＞1α,25(OH)2D3＝20 - 氧杂 - 1α,25(OH)2D3＝22 - 氧杂 - 1α(OH)D3＞1α(OH)D3＝20 - 氧杂 - 1α(OH)D3。22 - 氧杂 - 1α,25(OH)2D3在诱导体内初次免疫反应方面的效力约为1α,25(OH)2D3的50倍，但前者在诱导高钙血症方面的活性仅为后者的1/100。这些结果表明，维生素D化合物的免疫调节活性在体内可与其高钙血症作用在结构上相分离。
