Kageyama Yasunori, Kobayashi Hayato, Kato Norihiko, Shimazu Masahiro
Department of Orthopaedic Surgery, Heisei Memorial Hospital, 123-1 Mizugami, Fujieda 426-8662, Japan.
Mod Rheumatol. 2009;19(4):372-8. doi: 10.1007/s10165-009-0175-z. Epub 2009 May 21.
This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-alpha (TNF-alpha) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-alpha were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-alpha induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-alpha may induce granzyme B and RANTES production in RA patients.
本研究旨在分析可溶性肿瘤坏死因子-α（TNF-α）受体依那西普对类风湿关节炎（RA）患者血清中多种趋化因子水平的影响，这些趋化因子包括单核细胞趋化蛋白-1（MCP-1）、活化正常T细胞表达和可能分泌的调节因子（RANTES）以及颗粒酶B。28例RA患者接受依那西普每周一次或两次治疗，疗程超过6个月。在基线以及初始治疗后3个月和6个月时测量临床和实验室参数，并使用酶联免疫吸附测定（ELISA）试剂盒测定血清MCP-1、RANTES和颗粒酶B水平。此外，还测量了用TNF-α刺激的培养滑膜细胞产生的MCP-1、RANTES和颗粒酶B水平。在用依那西普初始治疗后3个月和6个月时，观察到血清MCP-1水平显著下降。血清RANTES和颗粒酶B水平未显示出显著变化。TNF-α可诱导RA患者培养的滑膜细胞产生MCP-1、RANTES和颗粒酶B。血清MCP-1水平与28个关节联合CRP疾病活动评分（DAS28-CRP）显著相关，表明MCP-1在类风湿性炎症发病机制中的作用。本研究表明，降低RA患者MCP-1的产生是依那西普新确定的一种作用。另一种与TNF-α无关的级联反应可能在RA患者中诱导颗粒酶B和RANTES的产生。
