Methotrexate-how does it really work?
Methotrexate-how does it really work?
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DOI：
10.1038/nrrheum.2010.5
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发表时间：
2010-03-01
影响因子：
33.7
通讯作者：
Cronstein, Bruce N.
中科院分区：
文献类型：
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作者：
Chan, Edwin S. L.;Cronstein, Bruce N.
甲氨蝶呤仍然是治疗类风湿性关节炎和其他风湿性疾病的基石。已知叶酸拮抗作用有助于抗增殖作用，这在甲氨蝶呤对抗恶性疾病的作用中是重要的，但同时给予叶酸或亚叶酸不会降低这种药物的抗炎潜力，这表明其他作用机制可能是有效的。虽然没有一种机制足以解释甲氨蝶呤的所有抗炎活性，但已在体外和体内证实腺苷从细胞中释放。甲氨蝶呤也可能通过抑制多胺而赋予抗炎特性。与腺苷释放相关的炎症生物学效应提供了对甲氨蝶呤如何发挥其对炎性疾病的作用的见解，同时导致其一些众所周知的不良反应。这些活动有助于复杂和多方面的机制，使甲氨蝶呤有效治疗炎症性疾病。
Methotrexate remains a cornerstone in the treatment of rheumatoid arthritis and other rheumatic diseases. Folate antagonism is known to contribute to the antiproliferative effects that are important in the action of methotrexate against malignant diseases, but concomitant administration of folic or folinic acid does not diminish the anti-inflammatory potential of this agent, which suggests that other mechanisms of action might be operative. Although no single mechanism is sufficient to account for all the anti-inflammatory activities of methotrexate, the release of adenosine from cells has been demonstrated both in vitro and in vivo. Methotrexate might also confer anti-inflammatory properties through the inhibition of polyamines. The biological effects on inflammation associated with adenosine release have provided insight into how methotrexate exerts its effects against inflammatory diseases and at the same time causes some of its well-known adverse effects. These activities contribute to the complex and multifaceted mechanisms that make methotrexate efficacious in the treatment of inflammatory disorders.