Recent studies have shown that the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), can affect both tissues and cells that are not directly involved in calcium homeostasis.
In particular, a role for calcitriol as a regulator of immune cell differentiation and proliferation has been proposed.
Specific high-affinity intracellular receptors for calcitriol (VDR) are detectable in activated T cells, and activated macrophages are able to synthesize calcitriol.
A possible paracrine mechanism of action has been postulated.
Vitamin D may therefore have a similar role to that of other immune regulatory molecules such as cytokines.
The precise interaction of calcitriol with the cytokine network is not yet fully defined, but its ability to modulate immune cells in vitro and its association with inflammatory diseases are now well documented.
These findings are outlined in this review with particular reference to effects on macrophages and lymphocytes.
Calcitriol and monocyte function
The secretory role of macrophages is central to the production of localized concentrations of calcitriol within immune microenvironments.
However, macro¬phages perform other functions which can also be modulated by calcitriol.
The hormone has been shown to stimulate both phagocytic and antibody-dependent macrophage cytotoxicity.
Rook et al. (1986) reported that calcitriol enhances the ability of macrophages to inhibit proliferation of Mycobacterium tuberculosis in vitro.
Other studies have shown that the hormone increases Fc receptor expression on mononuclear cells(Abe, Shiina, Miyaura et al. 1984), and can aid their protection in inflammatory environments by inducing expression of the heat shock protein (Polla, Healy, Amento & Krane, 1986).
Cells such as macrophages which are involved in presenting antigen are known as accessory cells.
Another important group of accessory cells are dendritic cells which express abundant VDR, further emphasizing a possible role for the hormone in antigen presentation (Brennan, Katz, Nunn et al. 1987).
Macrophages are derived from less mature myeloid stem cells which originally have a common pleuripotent cell origin and many groups including ours have examined the effect of vitamin D on stem cell development, in particular the mononuclear phago¬cyte system (Hewison, Barker, Brennan et al. 1989).
These studies have been greatly facilitated by the development of leukaemic cell lines from myeloid pre¬cursor cells.
It is not yet clear at which point in the stem cell pathway VDR induction occurs, but more mature cell lines such as HL 60 and U937 express these receptors and are responsive to calcitriol which stimulates differentiation towards macrophage-like cells (Karmali, Bhalla, Farrow et al. 1989).
Download Full Article