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  • Title: Effects of a single dose of methotrexate on 5- and 12-lipoxygenase products in patients with rheumatoid arthritis.
    Author: Leroux JL, Damon M, Chavis C, Crastes de Paulet A, Blotman F.
    Journal: J Rheumatol; 1992 Jun; 19(6):863-6. PubMed ID: 1328631.
    Abstract:
    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.
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