ENHANCEMENT OF LEUKOTRIENE A(4) 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 A(4) (LTA(4)) followed by predominant non-enzymatic LTA(4) opening and leukotriene B-4 (LTB(4)) 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.