Vitamin D and the immune system.

The investigation of the potential influence of 1,25-(OH)2D3 on immune cells has expanded our understanding of hormone-cytokine interactions. 1,25-(OH)2D3 stimulates phenotypic and function changes in immature monocytes, alters protein synthesis, increases adherence, and augments interleukin-1 secretion. T lymphocyte proliferation and B cell immunoglobulin production are inhibited by the hormone. 1,25-(OH)2D3 decreases IL 2 and IFN-gamma synthesis by activated T lymphocytes in association with decreases in mRNA for these proteins. The step from the investigation of in vitro interactions to an understanding of in vivo effects of 1,25-(OH)2D3 on immune cells requires further study. On the basis of information at hand, such as the potential for macrophage conversion of 25-OH-D3 to 1,25-(OH)2D3, decreased or increased macrophage function in association with vitamin D3 status in vitro and in vivo, as well as altered T cell subset ratios and proliferative responses with administration of the hormone, it is tempting to speculate that 1,25-(OH)2D3 exerts an influence on immune cell function in concert with other recognized soluble mediators of monocyte and lymphocyte origin. The primary influence of 1,25-(OH)2D3 may vary with the tissue site. Systemic levels of hormone may aid in maintaining tonic immunosuppression and thus prevent trivial antigenic stimuli from initiating an immune response. Upon initiation of an immune response to a significant antigenic challenge 1,25-(OH)2D3 may, in concert with other suppressor mechanisms, limit the extent of the host response by inhibition of IL 2 and IFN-gamma production. At local sites of chronic inflammation concentrations of 1,25-(OH)2D3 may be elevated and may act in an autocrine or paracrine fashion to alter the immune response, for example, by increasing IL 1 production and antigen presentation by tissue monocyte/macrophages. The activation of T cells is associated with the synthesis of 1,25-(OH)2D3 receptors, thus potentially limiting T cell proliferation in the presence of the hormone. Other biological actions of IL 1, however, including effects on cells in bone, joint, and brain may be augmented. Thus, the end result of the opposing effects of 1,25-(OH)2D3 on immune cells and their secretory products may vary with the specific cells involved, their state of maturation and activation, and the local concentrations of the hormone. Studies to date support the concept of an expanded role for 1,25-(OH)2D3 in immune cell biology.