雌激素干扰来氟米特对人激活单核细胞细胞因子产生的调节作用。

Estrogens interfere with leflunomide modulation of cytokine production by human activated monocytes.

机构信息

Research Laboratories and Clinical Academic Unit of Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy.

出版信息

Ann N Y Acad Sci. 2010 Apr;1193:30-5. doi: 10.1111/j.1749-6632.2009.05298.x.

DOI:10.1111/j.1749-6632.2009.05298.x

PMID:20398005

Abstract

Rheumatoid arthritis (RA) prevalence is greater in females than in males, supporting estrogens as modulators of immune response. Leflunomide (LEF) is employed in the RA treatment. We studied the combinatory effects of LEF active metabolite A77 1726 (LEF-M) and 17beta-estradiol (E2) on inflammatory cytokine production by cultured macrophages obtained from activated human monocytes (THP-1 cells). Macrophages were cultured with LEF-M alone and in combination with E2. IL-6, TNF-alpha, and TGF-beta were evaluated by immunocytochemistry (ICC), Western blot (WB), and reverse transcriptase-polymerase chain reaction (RT-PCR). ICC, as well as WB and RT-PCR, showed that LEF-M, in respect to untreated cells, significantly downregulated the cytokine production (IL-6 P < 0.01, TNF-alphaP < 0.001, TGF-betaP < 0.01). On the contrary, E2 increased the cytokine production, a result that was significantly reversed when LEF-M was subsequently added (IL-6, TNF-alpha, TGF-betaP < 0.001 vs. E2). E2 seems to contrast the LEF-M activity. These results might support a more efficient therapeutical effect of LEF in male with respect to female RA patients.

摘要

类风湿性关节炎（RA）的患病率在女性中高于男性，这支持雌激素是免疫反应调节剂。来氟米特（LEF）用于 RA 的治疗。我们研究了 LEF 的活性代谢物 A771726（LEF-M）和 17β-雌二醇（E2）对从激活的人单核细胞（THP-1 细胞）获得的培养巨噬细胞产生的炎症细胞因子的组合作用。巨噬细胞用 LEF-M 单独培养，并与 E2 联合培养。通过免疫细胞化学（ICC）、Western blot（WB）和逆转录-聚合酶链反应（RT-PCR）评估 IL-6、TNF-α 和 TGF-β。ICC 以及 WB 和 RT-PCR 显示，与未处理的细胞相比，LEF-M 显著地下调了细胞因子的产生（IL-6 P <0.01，TNF-αP <0.001，TGF-βP <0.01）。相反，E2 增加了细胞因子的产生，当随后添加 LEF-M 时，这种作用明显逆转（IL-6、TNF-α、TGF-βP <0.001 与 E2 相比）。E2 似乎与 LEF-M 的活性相反。这些结果可能支持 LEF 在男性 RA 患者中的治疗效果优于女性。