Martínez-Osuna P, Zwolinska J B, Sikes D H, Cory J G, Silveira L H, Jara L J, Espinoza L R
Department of Medicine, Louisiana State University Medical Center, New Orleans 70112.
Clin Exp Rheumatol. 1993 May-Jun;11(3):249-53.
Whether methotrexate (MTX) is effective in rheumatoid arthritis (RA) because of immunosuppressive and/or anti-inflammatory mechanisms of action is controversial. Many lines of investigation point to the latter. We evaluated DNA synthesis in peripheral blood lymphocytes (PBL) from 33 RA patients on oral MTX (7.5-15 mg/wk) and in 30 healthy controls by flow cytometric cell cycle analysis (CCA). DNA synthesis was also evaluated with a thymidilate synthetase activity assay (TSA) (3H-deoxyuridine incorporation) in 12 patients and 21 controls (12 on MTX and NSAID, and 9 healthy subjects). The patients had taken MTX for at least 3 months and were in different stages of clinical activity. There were no significant differences in TSA or in the cell cycle phase distributions (especially the S phase) between treated RA patients and controls. These data suggest that low-dose oral MTX does not inhibit DNA synthesis and therefore does not have an immunosuppressive effect on lymphocytes from patients with RA.
甲氨蝶呤（MTX）治疗类风湿性关节炎（RA）时，其有效性究竟是源于免疫抑制和/或抗炎作用机制，这一问题存在争议。诸多研究线索指向后者。我们通过流式细胞术细胞周期分析（CCA），对33例口服MTX（7.5 - 15毫克/周）的RA患者及30例健康对照者外周血淋巴细胞（PBL）中的DNA合成情况进行了评估。同时，还采用胸苷酸合成酶活性测定法（TSA）（³H - 脱氧尿苷掺入法）对12例患者和21例对照者（12例服用MTX和非甾体抗炎药，9例健康受试者）的DNA合成情况进行了评估。这些患者服用MTX至少3个月，且处于不同的临床活动阶段。在TSA或细胞周期阶段分布（尤其是S期）方面，接受治疗的RA患者与对照者之间并无显著差异。这些数据表明，低剂量口服MTX不会抑制DNA合成，因此对RA患者的淋巴细胞没有免疫抑制作用。
