甲氨蝶呤（MTX）对类风湿关节炎（RA）患者信号淋巴细胞激活分子（SLAM）表达的影响及其在细胞因子产生调节中的作用。
The effect of methotrexate (MTX) on expression of signalling lymphocytic activation molecule (SLAM) in patients with rheumatoid arthritis (RA) and its role in the regulation of cytokine production.
作者信息
Morita Y, Fukazawa T, Hirashima M, Kaga K, Kusaoi M, Morita T, Touyama S, Morita K, Takasaki Y, Hashimoto H
机构信息
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
出版信息
Scand J Rheumatol. 2006 Jul-Aug;35(4):268-72. doi: 10.1080/03009740600588186.
OBJECTIVE
To investigate the effect of methotrexate (MTX) on cytokine production by activated CD4+ T-cells in patients with rheumatoid arthritis (RA).
METHODS
The effect of MTX on intracellular expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), and cell surface expression of signalling lymphocytic activation molecule (SLAM) from freshly isolated peripheral blood mononuclear cells (PBMCs), and after in vitro culture with or without MTX, was analysed with flow cytometry in 18 patients with RA and 20 healthy controls.
RESULTS
Intracellular expression of IFN-gamma and IL-4 on freshly isolated CD4+ T-cells was significantly higher in patients with RA than in the controls (p<0.05). Intracellular expression of both IFN-gamma and IL-4 after culture with MTX was significantly lower than those after culture without MTX in patients with RA. Although no significant difference was observed in SLAM expression on freshly isolated CD4+ T-cells between patients with RA and the controls, MTX significantly decreased SLAM expression on both activated IFN-gamma+ and IL-4+CD4+ T-cells in patients with RA.
CONCLUSION
In vitro modulation of the cytokine network by MTX, IFN-gamma, and IL-4 is one of the major targets for MTX, and production of IFN-gamma and IL-4 by PBMCs may be suppressed by SLAM on activated CD4+ T-cell in patients with RA.
目的
研究甲氨蝶呤（MTX）对类风湿关节炎（RA）患者活化CD4 + T细胞细胞因子产生的影响。
方法
采用流式细胞术分析18例RA患者和20例健康对照者新鲜分离的外周血单个核细胞（PBMC），以及在有或无MTX体外培养后，MTX对干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）细胞内表达，和信号淋巴细胞激活分子（SLAM）细胞表面表达的影响。
结果
RA患者新鲜分离的CD4 + T细胞上IFN-γ和IL-4的细胞内表达显著高于对照组（p<0.05）。RA患者MTX培养后IFN-γ和IL-4的细胞内表达均显著低于无MTX培养后。虽然RA患者与对照组新鲜分离的CD4 + T细胞上SLAM表达无显著差异，但MTX显著降低RA患者活化的IFN-γ +和IL-4 + CD4 + T细胞上的SLAM表达。
结论
MTX对细胞因子网络的体外调节，IFN-γ和IL-4是MTX的主要作用靶点之一，RA患者PBMC产生的IFN-γ和IL-4可能被活化CD4 + T细胞上的SLAM抑制。
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