The effect of methotrexate on lipoxygenase metabolism in neutrophils from rats:In vitro andex vivo studies

Studies were undertaken to examine the effect of methotrexate (MTX) administeredin vivo or addedin vitro upon the production of the 5-lipoxygenase (5-LO) metabolites of arachidonic acid (AA) by rat neutrophils. Peptone-induced peritoneal exudate cells were stimulated by A23187 and the cell suspensions assayed for leukotriene B₄ (LTB₄), the all-trans isomers of LTB₄ and 5-hydroxyeicosatetraenoic acid (5-HETE) using high-pressure liquid chromatography. MTX addedin vitro to rat cells was weakly inhibitory; however, no inhibition of LTB₄ production was seen followingin vivo administration of MTX by oral, subcutaneous or intraperitoneal routes. On the basis of these findings, inhibition of 5-LO metabolism does not appear to explain the anti-inflammatory effects of MTX.