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目的 探讨普伐他汀对在免疫调控中起重要作用的人单核细胞源树突状细胞(DC)免疫功能的影响。方法 采用免疫磁珠法分离人外周血CD14+单核细胞,经含重组粒细胞巨噬细胞刺激因子(100 ng/ml)和重组白介素(rhIL) 4(20 ng/ml)的Cellgro培养,使其分化为DC。DC与50~100μmol/L普伐他汀孵育72 h后,采用流式细胞术检测DC表型(CD1a、CD40、CD86、HLA DR),混合T淋巴细胞反应检测DC对淋巴细胞增殖的影响,采用酶联免疫吸附试验法检测细胞培养上清液中Th1/Th2 [白介素(IL)- 12、干扰素(IFN) γ/ IL- 2、IL- 10]细胞因子的浓度。结果 与对照组相比,经普伐他汀处理的DC可下调CD80、CD86、HLA DR和CD1a的表达,对T淋巴细胞增殖作用明显减弱,明显抑制DC- Th1 细胞因子IL -12 和IFN -γ的分泌(P<0.05),但对Th2细胞因子IL -2 和IL -10水平无明显影响。100μmol/L甲羟戊酸可逆转普伐他汀的作用。结论 普伐他汀可明显抑制DC的成熟和免疫活性,此作用与甲羟戊酸途径有关。这可能是他汀类药物免疫调节的新机制。
Objective To investigate the effect of pravastatin on the immune function of human monocyte-derived dendritic cells (DCs), which plays an important role in the immune regulation. Methods Human peripheral blood CD14 + monocytes were isolated by immunomagnetic beads method and cultured in Cellgro containing recombinant granulocyte macrophage stimulating factor (100 ng / ml) and recombinant interleukin (rhIL) 4 (20 ng / ml) Differentiation into DC. DCs were incubated with 50-100 micromol / L pravastatin for 72 h. The DC phenotypes (CD1a, CD40, CD86, HLA DR) were detected by flow cytometry. The effect of DC on lymphocyte proliferation was examined by mixed T lymphocyte reaction. The concentrations of Th1 / Th2 [IL - 12, IFNγ / IL-2, IL-10] cytokines in cell culture supernatants were determined by enzyme-linked immunosorbent assay. Results Compared with the control group, pravastatin-treated DCs could down-regulate the expressions of CD80, CD86, HLA DR and CD1a, significantly attenuate the proliferation of T lymphocytes and significantly inhibit the expressions of IL-12 and IFN-γ (P <0.05), but had no significant effect on the levels of Th2 cytokines IL-2 and IL-10. 100μmol / L mevalonate can reverse the effect of pravastatin. Conclusions Pravastatin can significantly inhibit the maturation and immunological activity of DC, which is related to the mevalonate pathway. This may be a new mechanism of statin immune regulation.