Objective: To examine the effect of methotrexate (MTX) administered in vivo on the production of the 5-lipoxygenase (5-LO) metabolites of arachidonic acid by neutrophils from subjects with rheumatoid arthritis.
Methods: Neutrophils were isolated from peripheral blood samples taken 12 h before and 12 h after the ingestion of an oral dose of MTX and stimulated in vitro by calcium ionophore A23187. Lipid extracts of cell suspensions were assayed for leukotriene B4 (LTB4), the all-trans isomers of LTB4, 20-hydroxy LTB4 and 5-hydroxyeicosatetraenoic acid by high pressure liquid chromatography.
Results: An increase in the production of all measured 5-LO metabolites was seen between the pre and postdose assessments.
Conclusion: Our results do not support the putative inhibitory effect of MTX on 5-LO metabolism.