Egan L J, Sandborn W J
Inflammatory Bowel Disease Clinic, Mayo Clinic Rochester, MN 55905, USA.
Mayo Clin Proc. 1996 Jan;71(1):69-80. doi: 10.4065/71.1.69.
To review the limited published experience with methotrexate treatment for inflammatory bowel disease, to examine the proposed anti-inflammatory and immune-modifying mechanism of action and pharmacologic properties of methotrexate, and to detail its limiting toxicities.
A comprehensive synopsis of methotrexate is presented to aid physicians who treat patients with inflammatory bowel disease.
Methotrexate and its polyglutamate metabolites are folic acid analogues with inhibitory activity against many enzymes in the metabolic pathway of folic acid. Long-term low-dose methotrexate therapy (25 mg or less once a week) inhibits production of thymidylate, purines, and methionine and leads to accumulation of adenosine, a potent anti-inflammatory substance. These actions inhibit cellular proliferation, decrease formation of antibodies, and decrease production of mediators of inflammation such as interleukins and eicosanoids. Three uncontrolled trials and two controlled trials have demonstrated efficacy of low-dose methotrexate therapy for induction of remission in Crohn's disease and have also suggested possible benefit for ulcerative colitis and for remission maintenance indications in both diseases. Although methotrexate is generally well tolerated for long-term use at a low dose, several serious toxicities potentially limit its use.
Methotrexate is a promising new agent for the treatment of inflammatory bowel disease.
回顾甲氨蝶呤治疗炎症性肠病有限的已发表经验，研究其抗炎和免疫调节作用机制及药理学特性，并详述其局限性毒性。
呈现甲氨蝶呤的全面综述，以帮助治疗炎症性肠病患者的医生。
甲氨蝶呤及其聚谷氨酸代谢产物是叶酸类似物，对叶酸代谢途径中的许多酶具有抑制活性。长期低剂量甲氨蝶呤治疗（每周一次25毫克或更低剂量）可抑制胸苷酸、嘌呤和蛋氨酸的生成，并导致腺苷积累，腺苷是一种有效的抗炎物质。这些作用抑制细胞增殖，减少抗体形成，并减少炎症介质如白细胞介素和类花生酸的产生。三项非对照试验和两项对照试验已证明低剂量甲氨蝶呤治疗对克罗恩病诱导缓解有效，也提示对溃疡性结肠炎以及两种疾病的缓解维持可能有益。尽管甲氨蝶呤长期低剂量使用一般耐受性良好，但几种严重毒性可能限制其使用。
甲氨蝶呤是治疗炎症性肠病的一种有前景的新药。
