[Effects of methotrexate on leukotriene and derivated lipoxygenase synthesis in polynuclear neutrophils in rheumatoid polyarthritis].

Methotrexate (MTX) has been proved to be effective in rheumatoid arthritis (RA). The mechanism of action of MTX in this disease remains unelucidated but may involve inhibition of the enzyme 5-lipoxygenase. Arachidonic acid metabolites were studied in eight patients with active RA immediately prior to and 24 hours after the first intramuscular injection of 10 mg MTX. None of the patients were taking corticosteroids. Nonsteroidal antiinflammatory drugs were withdrawn four days before the study. Reverse phase high-performance liquid chromatography was used to quantitate metabolites produced by 5-lipoxygenase (5-LO) and 12-LO in plasma (full spectrum of blood cells) and purified neutrophils (PN) after stimulation with calcium ionophore A 21387 (50 microM for 30 minutes and 5 microM for 5 minutes, respectively). LTB4 production by PNs was significantly decreased (-32%, p < 0.01) 24 hours after MTX administration. A moderate (-17%), nonsignificant (NS) fall in LTB4 omega-oxidation products (wP) was seen. Production of 5-HETE was also slightly decreased (-15%, NS). Findings in plasma were comparable, with a significant decrease in total LTB4 (-29.8%, p < 0.01) and moderate falls in wP (-18.8%, NS) and in 5-HETE production (-17%, NS). Production of 12-HETE was unchanged. These findings suggest that MTX in a single dose is responsible for a decrease in the synthesis of LTB4 and 5-LO products in neutrophils and other blood cells in RA patients but does not affect 12-LO activity.