Effect of vitamin D deficiency on macrophage and lymphocyte function in the rat

Vitamin D deficiency has pronounced growth retardation effects on the skeletal system. Because the immune system has been implicated in the regulation of bone metabolism, we examined the effect of vitamin D deficiency on the functional development of immune function in a rachitic rat model. Rats deprived of vitamin D3 both in utero and in postnatal life (-/-) had significantly reduced thymocyte or splenocyte [3H]-thymidine incorporation to mitogens and decreased macrophage chemotaxis when compared with vitamin D3-sufficient rats (+/+). Rats that were deficient in vitamin D3 only during in utero development (-/+) or during postnatal life (+/-) tended to have [3H]thymidine incorporation levels that were intermediate to those of the -/- and +/+ group. Similarly, the chemotactic response of macrophages from the +/- and -/+ groups was intermediate to that of the -/- and +/+ group, except at high concentrations of C5a in which there was an overlap with the +/+ group. Interestingly, secretion of soluble mediators, including interleukin 2 by lymphocytes and interleukin 1 and PGE2 by macrophages, was unaffected by vitamin D deficiency. These results suggest that vitamin D3 is essential for the normal development of certain biological responses of lymphocytes and macrophages. Moreover, this rachitic rat model system will enable further evaluation of the role of vitamin D in the functional development of the cells of the immune system and their relationship to skeletal growth.