Enhancement of leukotriene A4 biosynthesis in neutrophils from patients with rheumatoid arthritis after a single glucocorticoid dose.
Human blood polymorphonuclear cells (PMN) from seven patients with active rheumatoid arthritis (RA) were compared for their capacities to produce leukotrienes ex vivo before (D0) and 24 hr (D1) after glucocorticoid pulse therapy. The present study shows for the first time that endogenous arachidonic acid metabolism via 5-lipoxygenase pathway is significantly increased after glucocorticoid administration, leading to increased generation of the unstable precursor leukotriene A4 (LTA4) followed by predominant non-enzymatic LTA4 opening and leukotriene B4 (LTB4) omega-hydroxylation pathway. These results are unexpected since usually glucocorticoids are usually thought to decrease inflammatory mediator biosynthesis and, moreover, they work to the detriment of the clinical improvement of the patient. The results are discussed in terms of product inactivation and cellular cooperation with monocytes and endothelial cells.
Service de Réadaptation Fonctionnelle, CHU Lapeyronie, Montpellier, France.
E
E
Thomas
J L
JL
Leroux
F
F
Blotman
B
B
Descomps
C
C
Chavis
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D017572:Leukotriene A4 / Q000096:biosynthesis*; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*
D005938:Glucocorticoids; D017572:Leukotriene A4; D007975:Leukotriene B4; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase