The effect of methotrexate on ex vivo lipoxygenase metabolism in neutrophils from patients with rheumatoid arthritis.
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.


CONCLUSIONS
Our results do not support the putative inhibitory effect of MTX on 5-LO metabolism.
Hawkes
J S
JS
Rheumatology Unit, Royal Adelaide Hospital, Australia.
Cleland
L G
LG
Proudman
S M
SM
James
M J
MJ
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism*; D008727:Methotrexate / Q000627:therapeutic use*; D009504:Neutrophils / Q000201:enzymology*
D008084:Lipoxygenase; D008727:Methotrexate