Immunosuppressive activity of 1 25-Dihydroxyvitamin D3 and analogs: from the cell to the human.

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 5 (V 3). 1998;

Abstract: Department of Pediatrics University of California San Diego The active vitamin D metabolite 1 25-Dihydroxyvitamin D3 [1 25-D3] exerts immunosuppressive activity in vitro and in vivo. The steroid inhibits lymphocyte proliferation and immunoglobulin production. More specifically 1 25-D3 directly inhibits IFN-secretion while it has no effect on IL-4 secretion. The sterol also inhibits the secretion of IL-12 a cytokine produced by antigen-presenting cells (monocytes and B cells) leading to the activation of helper T cell type 1 (Th 1). In animal models 1 25-D3 prevents the induction of spontaneous and induced autoimmune diseases such as experimental autoimmune encephalomyelitis lupus and diabetes. The doses required for optimal activity are supra physiologic but in recent years analogs of 1 25-D3 with similar immune suppression but reduced calcemic activity have been developed and have allowed for better tolerance and prolonged therapy in the animals. It appears that some target tissues might be more susceptible to the action of the drug e. g. the skin lesions could be completely prevented in experimental lupus of MRL mice while the glomerulonephritis could only be partially suppressed. In humans while the daily administration of 1 25-D3 for the treatment of renal osteodystrophy is current the systemic administration of the drug for immunosuppressive activity is limited. Topically a 1 25-D3 analog calcipotriol has been effective in the treatment of psoriasis. Systemically the hormone given to patients with severe psoriasis at dosages up to 1.27 ug per day has also been effective in controlling the disease with minimal calcemic effect but for limited periods of time. Recently 1 25-D3 has been effective in the treatment of skin lesions of a child with systemic scleroderma. ... le

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