Paricalcitol reduces basal and lipopolysaccharide-induced (LPS) TNF-α and IL-8 production by human peripheral blood mononuclear cells

Paricalcitol reduces basal and lipopolysaccharide-induced (LPS) TNF-α and IL-8 production by human peripheral blood mononuclear cells
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DOI:
10.1007/s11255-009-9541-1
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发表时间:
2010-03-01
影响因子:
2
通讯作者:
Galaktidou, Grammati
Galaktidou, Grammati
中科院分区:
医学4区
文献类型:
--
作者:
Eleftheriadis, Theodoros;Antoniadi, Georgia;Galaktidou, Grammati

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维生素D及其类似物被证明具有免疫调节作用。Paricalcitol是一种安全的维生素D类似物。多年来,它一直用于治疗血液透析患者的继发性甲状旁腺功能亢进症,重要的是,它比维生素d的钙化程度低。在本研究中,我们在体外评估了paricalcitol的免疫调节/抗炎特性。10名健康志愿者参加了这项研究。以每孔10(6)个细胞的浓度培养外周血单个核细胞(PBMC),在存在或不存在脂多糖(LPS) (100 ng/ml)和不存在特立醇(10(-8)M)的条件下培养48小时。ELISA法检测上清液中tnf - α和IL-8的含量。paricalcitol (44.1 +/- A 23.2 pg/ml)降低了基础tnf - α浓度(50.3 +/- A 22 pg/ml)。脂多糖使tnf - α浓度升高(150.0 +/- A 81.7 pg/ml),而特icalcitol使其降低(121.1 +/- A 69.0 pg/ml)。白藜芦醇对IL-8产生的影响更为深远。paricalcitol (1273 +/- A 472 pg/ml)降低了基础IL-8浓度(1926 +/- A 455 pg/ml)。LPS使IL-8浓度升高(2361 +/- A 385 pg/ml),而paricalcitol使其恢复到基础水平(1849 +/- A 417 pg/ml)。paricalcitol对转化生长因子α和白细胞介素8的体外抑制证实了这种维生素D类似物的免疫调节特性。
Vitamin D and its analogues proved to exert immunomodulatory effects. Paricalcitol is a vitamin D analogue that is safe. It has been used for years in the treatment of secondary hyperparathyroidism in hemodialysis patients and, importantly, it is less calcemic than vitamin D. In this study the immunomodulatory/anti-inflammatory properties of paricalcitol were evaluated in vitro.Ten healthy volunteers enrolled into the study. Peripheral blood mononuclear cells (PBMC) at a concentration of 10(6) cells per well were cultured for 48 h in the presence or not of lipopolysaccharide (LPS) (100 ng/ml) and in the presence or not of paricalcitol (10(-8) M). TNF-alpha and IL-8 were measured in the supernatants by ELISA.Basal TNF-alpha concentration (50.3 +/- A 22 pg/ml) was reduced by paricalcitol (44.1 +/- A 23.2 pg/ml). LPS increased TNF-alpha concentration (150.0 +/- A 81.7 pg/ml), but paricalcitol reduced it (121.1 +/- A 69.0 pg/ml). The effect of paricalcitol on IL-8 production was more profound. Basal IL-8 concentration (1926 +/- A 455 pg/ml) was reduced by paricalcitol (1273 +/- A 472 pg/ml). LPS increased IL-8 concentration (2361 +/- A 385 pg/ml), but paricalcitol returned it to its basal level (1849 +/- A 417 pg/ml).The in vitro inhibition of transforming growth factor alpha and interleukin 8 by paricalcitol confirms the immunomodulatory properties of this vitamin D analogue.