Wascher T C, Hermann J, Brezinschek H P, Brezinschek R, Wilders-Truschnig M, Rainer F, Krejs G J
Medizinische Universitätsklinik, Karl-Franzens-Universität Graz, Austria.
Clin Investig. 1994 Jul;72(7):535-40. doi: 10.1007/BF00207484.
The mode of action of methotrexate in the treatment of rheumatoid arthritis is still questionable. Although in vitro results suggest an immunosuppressive effect of methotrexate, several clinical studies have failed to confirm these effects in patients treated with oral low-dose methotrexate. With respect to the highly variable bioavailability of methotrexate, we investigated the effects of an intravenous administration of 15 mg methotrexate per week on peripheral blood lymphocyte subsets in eight patients with rheumatoid arthritis. Methotrexate after 12 weeks significantly (P < 0.01) reduced total peripheral blood lymphocytes and led to a pronounced redistribution of lymphocyte subsets with a preferred reductive effect on B-lymphocytes (P < 0.005) and T-lymphocytes (P < 0.05). Natural killer cells and killer cell-like T cells, on the other hand, were unaffected by the treatment. Our results suggest a cell-type specific effect of intravenously administered low-dose methotrexate on peripheral blood lymphocytes. This effect, in our opinion, may contribute to the mode of action of methotrexate as an immunosuppressive drug in the treatment of rheumatoid arthritis.
甲氨蝶呤治疗类风湿性关节炎的作用机制仍存在疑问。尽管体外实验结果表明甲氨蝶呤具有免疫抑制作用，但多项临床研究未能证实口服低剂量甲氨蝶呤治疗的患者有这些效果。鉴于甲氨蝶呤的生物利用度高度可变，我们研究了每周静脉注射15毫克甲氨蝶呤对8例类风湿性关节炎患者外周血淋巴细胞亚群的影响。12周后，甲氨蝶呤显著（P<0.01）减少了外周血淋巴细胞总数，并导致淋巴细胞亚群明显重新分布，对B淋巴细胞（P<0.005）和T淋巴细胞（P<0.05）有优先的减少作用。另一方面，自然杀伤细胞和杀伤细胞样T细胞不受该治疗的影响。我们的结果表明静脉注射低剂量甲氨蝶呤对外周血淋巴细胞有细胞类型特异性作用。我们认为，这种作用可能有助于解释甲氨蝶呤作为免疫抑制药物治疗类风湿性关节炎的作用机制。
