Fujibayashi S, Suzuki S, Okano K, Naitoh T, Katabami T, Someya K
Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Immunol Lett. 1991 Nov;30(3):307-11. doi: 10.1016/0165-2478(91)90043-a.
The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue 22-oxacalcitriol (OCT), which was reported to have very weak bone resorbing activity, on the production of tumor necrosis factor (TNF)-alpha was investigated. Mononuclear cells (MNC; 10(6)/ml) were incubated in 5% FCS/RPMI-1640 medium containing 1 microgram/ml lipopolysaccharide (LPS) in the presence or absence of 10(-8) M 1,25(OH)2D3 or 10(-8) M OCT for up to 96 h. Both 1,25(OH)2D3 and OCT suppressed TNF-alpha release by LPS-stimulated mononuclear cells, from the early to late stage of the incubation period, while neither 1,25(OH)2D3 nor OCT shifted the peak time point of TNF-alpha release clearly. MNC (10(6)/ml) were incubated with 1 microgram of LPS in the presence of various concentrations of 1,25(OH)2D3 or 10(-8) M OCT for 48 h. 1,25(OH)2D3 reduced TNF-alpha levels of LPS-stimulated MNC culture supernatant at 48 h in a dose-dependent manner. The half-maximal dose (ED50) for this suppressive effect was 3.7 x 10(-9) M. OCT decreased TNF-alpha levels of culture supernatant at 48 h with a half-maximal dose of 7.8 x 10(-11) M, which indicates that it is approximately 50 times more potent than that of 1,25(OH)2D3. These results indicate that OCT may be applicable as an immunosuppressive agent with limited calcium metabolic activity.
研究了1,25 - 二羟基维生素D3（1,25(OH)2D3）及其类似物22 - 氧杂骨化三醇（OCT，据报道其具有非常弱的骨吸收活性）对肿瘤坏死因子（TNF）-α产生的影响。单核细胞（MNC；10⁶/ml）在含有1μg/ml脂多糖（LPS）的5%胎牛血清/RPMI - 1640培养基中孵育，分别加入或不加入10⁻⁸M的1,25(OH)2D3或10⁻⁸M的OCT，孵育长达96小时。1,25(OH)2D3和OCT在孵育期的早期到晚期均抑制LPS刺激的单核细胞释放TNF -α，而1,25(OH)2D3和OCT均未明显改变TNF -α释放的峰值时间点。将MNC（10⁶/ml）与1μg的LPS在不同浓度的1,25(OH)2D3或10⁻⁸M的OCT存在下孵育48小时。1,25(OH)2D3以剂量依赖的方式降低了48小时时LPS刺激的MNC培养上清液中的TNF -α水平。这种抑制作用的半数有效剂量（ED50）为3.7×10⁻⁹M。OCT在48小时时降低了培养上清液中的TNF -α水平，半数有效剂量为7.8×10⁻¹¹M，这表明其效力约为1,25(OH)2D3的50倍。这些结果表明，OCT可能作为一种钙代谢活性有限的免疫抑制剂适用。
