Zeller J M, Gudewicz P W
J Immunopharmacol. 1981;3(3-4):309-21. doi: 10.3109/08923978109031064.
Methotrexate (MTX) is widely used in cancer chemotherapy, although the effects of MTX on cellular antitumor defense mechanisms are poorly understood. To evaluate the effect of MTX on the cellular inflammatory response, male Sprague-Dawley rats were treated with four daily i.p. injections of MTX or a control vehicle. Rats treated with daily doses of 1.2 mg/kg MTX demonstrated a significant reduction in number of peritoneal exudate cells, specifically macrophages, collected 96 hours following the inflammatory stimulus. To determine if metabolic perturbations also occur upon exposure to MTX, glucose oxidation and protein synthesis by inflammatory cells were monitored in vitro. At a MTX concentration of 10(-3)M, peritoneal exudate cell 14C-1-glucose and 14C-6-glucose oxidation was significantly depressed. 14C-1-leucine incorporation into TCA precipitable protein was inhibited at 4 x 10(-3)M MTX. Peritoneal exudate cell viability was not altered at these concentrations of MTX. These results demonstrate that MTX, at therapeutic concentrations, can depress the influx of macrophages to a inflammatory site and also diminish energy metabolism and protein synthesis by inflammatory cells.
甲氨蝶呤（MTX）广泛应用于癌症化疗，尽管MTX对细胞抗肿瘤防御机制的影响尚不清楚。为了评估MTX对细胞炎症反应的影响，对雄性Sprague-Dawley大鼠进行腹腔注射，每日一次，连续四天注射MTX或对照载体。每日剂量为1.2mg/kg MTX的大鼠在炎症刺激后96小时收集的腹腔渗出细胞（特别是巨噬细胞）数量显著减少。为了确定暴露于MTX时是否也会发生代谢紊乱，在体外监测炎症细胞的葡萄糖氧化和蛋白质合成。在MTX浓度为10（-3）M时，腹腔渗出细胞14C-1-葡萄糖和14C-6-葡萄糖氧化显著降低。在4×10（-3）M MTX时，14C-1-亮氨酸掺入三羧酸循环可沉淀蛋白受到抑制。在这些MTX浓度下，腹腔渗出细胞活力未改变。这些结果表明，在治疗浓度下，MTX可抑制巨噬细胞向炎症部位的流入，并减少炎症细胞的能量代谢和蛋白质合成。
