Regulation of macrophage growth responses to colony-stimulating factor-1 by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has previously been shown to affect the biology of a variety of immune cells, including the functions of macrophages. The effect of the vitamin D metabolite on the proliferative responses of macrophages to the cytokine colony-stimulating factor-1 (CSF-1) has been studied. It was found that this substance was able to suppress the growth responses of macrophages to CSF-1 as assessed by macrophage-tritiated thymidine uptake and also by cell counts. The effect was specific to this vitamin D metabolite because another vitamin D analogue, 25 hydroxyvitamin D3, did not have a similar effect on the responses of such cells to CSF-1. The results yield information on the regulatory role of 1,25(OH)2D3 on macrophage growth. It would appear that this vitamin D metabolite may act as a negative autoregulatory cytokine because it is produced by the macrophage when it is activated. A schema can be envisaged where CSF-1 is delivered to the macrophage to activate it and to cause it to proliferate. In the process, it also secretes 1,25(OH)2D3, which exerts a suppressive action to dampen this response.