Leroux J L, Damon M, Chavis C, Crastes de Paulet A, Blotman F
Department of Physical Medicine, Faculte de Medecine, Hôpital Lapeyronie, Montpellier, France.
J Rheumatol. 1992 Jun;19(6):863-6.
The inhibition of 5-lipoxygenase could be involved in the mechanism of action of methotrexate (MTX). We studied 8 patients with active rheumatoid arthritis (RA) immediately before and the day after the first dose of MTX (10 mg intramuscularly). Leukotriene B4 (LTB4) formation by polymorphonuclear leukocytes was significantly decreased (32%, p less than 0.01). This essentially involved released LTB4. A slight decrease was also obtained in omega-oxidation products. Similar results were obtained for plasma LTB4 (30%, p less than 0.02). A non-significant decrease in 5-HETE was noted. Conversely, 12-HETE was not modified. Our results suggest MTX has an effect on the 5-lipoxygenase pathway, particularly at the LTA4 epoxide hydrolase step, since 5-HETE and 6-trans-LTB4 isomers are not involved.
5-脂氧合酶的抑制作用可能参与了甲氨蝶呤(MTX)的作用机制。我们研究了8例活动期类风湿关节炎(RA)患者,在首次注射MTX(10mg肌肉注射)前及注射后当天进行观察。多形核白细胞生成白三烯B4(LTB4)的量显著减少(32%,p<0.01)。这主要涉及释放的LTB4。ω-氧化产物也有轻微减少。血浆LTB4也得到了类似结果(30%,p<0.02)。5-羟二十碳四烯酸(5-HETE)有不显著的减少。相反,12-HETE未发生改变。我们的结果表明MTX对5-脂氧合酶途径有影响,特别是在LTA4环氧水解酶步骤,因为5-HETE和6-反式-LTB4异构体未参与其中。