부산대학교 도서관

The biologic role of 1,25-dihydroxyvitamin D3, such as anti-inflammatory functions, reduction of cytokine production by T cells and immunoglobulin production by B cells, is well established. However, its clinical use as an immunosuppressive agent is limited because of the hypercalcemic toxicity occurring after systemic application. The purpose of this study was to investigate the immunmodulatory effects of 22-ene-25-oxa-vitamin D (ZK156979), a novel low calcemic vitamin D analogue.Human peripheral blood mononuclear cells (PBMCs) from healthy donors were isolated using the Ficoll Hypaque technique, cultured for 24 h and treated with different concentrations of ZK156979 ranging from 10−5 to 10−10 mol L−1 compared with 1,25-dihydroxyvitamin D3[10−5−10−10 mol L−1] following phytohaemagglutinin (PHA) stimulation. Interferon gamma (IFNγ), tumour necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), interleukin 10 (IL-10) and interleukin 4 (IL-4) secretion in supernatants were measured by ELISA.ZK156979 inhibited the PHA-induced Th1-response (IFNγ and TNFα levels) and the macrophage-product IL-1β in a concentration-dependent manner (10−10−10−5 mol L−1) with the efficiency on cytokine expression compared with 1,25-dihydroxyvitamin D3 being slightly reduced. In contrast, ZK156979 and 1,25-dihydroxyvitamin D3 both affected the Th2 response, leading to significantly increased IL-10- and IL-4 secretion.ZK156979 is a member of novel vitamin D analogues revealing prominent immunomodulatory and suppressive characteristics with distinctive inhibition of Th1-cytokines whereas the Th2 compartment is augmented, thus providing a considerable therapeutic potential in T-cell -mediated diseases.Eur J Clin Invest 2005; 35 (5): 343 –349 [ABSTRACT FROM AUTHOR]