曲古抑菌素A对SLE患者外周血IL-10和IL-12分泌的影响

Role of histone deacetylase inhibitors on the excretion of IL-10 and IL-12 in the patients with SLE

目的:探讨组蛋白去乙酰化酶(HDAC)抑制剂对系统性红斑狼疮(SLE)患者外周血全血培养细胞中IL-10和IL-12分泌水平的影响。方法:选取21例SLE患者和10名正常人,采集空腹静脉血标本分为空白组、HDAC抑制剂(曲古抑菌素A,TSA)组、植物血球凝集素/脂多糖(PHA/LPS)刺激组和PHA/LPS+TSA组作体外全血细胞培养,分离培养液上清并应用酶联免疫吸附法(ELISA)检测IL-10和IL-12分泌水平。结果:SLE患者的外周血全血培养细胞IL-12分泌水平明显低于正常人(P<0.01),但IL-10却明显高于正常人(P<0.01);TSA对SLE患者IL-10的分泌有显著抑制作用(P<0.01),而对IL-12则有明显上调作用(P<0.01),但对正常人IL-10和IL-12分泌水平无明显影响;而且SLE患者IL-10和IL-12的分泌水平分别与SLE疾病活动指数(SLEDAI)呈不同程度的正相关和负相关。结论:IL-10分泌水平上调和IL-12下降在SLE的发病中可能起重要作用,TSA对体外培养的外周血多途径激活后的IL-10分泌具有抑制作用,对IL-12具有上调作用,HDAC抑制剂可能是治疗SLE的一种新方法。

Objective： To explore the effect of histone deacetylase inhibitors on the excretion levels of IL - 10 and IL- 12 in patients with SLE. Methods： Twenty- one patients with SLE and 10 heathy volunteers were involved. Peripheral blood samples were collected and cultured with or without PHA/LPS, TSA and PHA/LPS ＋ TSA. After 24 hours of culture, IL- 10 and IL- 12 in euhure supematant were measured by ELISA. Results. The excretion levels of IL - 12 in SLE were significantly lower than those in normal controls （ P 〈 0.01 ）, but IL- 10 were significantly higher than nomral controls （ P 〈 0.01 ）, and the levels of IL - 10 and IL - 12 were positive and negative correlated with SLE disease active index （SLEDAI） respectively. TSA could inhibit the excretion of IL- 10 significantly （ P 〈 0.01 ） and promote the excretion of IL - 12 significantly （ P 〈 0.01 ）. Furthemlore, TSA could not affect the excretion of IL- 10 and IL- 12 in normal controls. Conclusion： Elevated excretion of IL- 10 and depressed IL- 12 in patients with SLE may play an important role in the disease pathogenesis, and TSA may be a new option for the treatment of SLE.