leukotriene-a4 and Arthritis--Rheumatoid

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.

Topics: Arachidonate 5-Lipoxygenase; Arachidonic Acid; Arthritis, Rheumatoid; Female; Glucocorticoids; Humans; Leukotriene A4; Leukotriene B4; Male; Middle Aged; Neutrophils

The synthesis of products of the 5-lipoxygenase pathway by synovial fluid (SF) and peripheral blood neutrophils of 12 patients with rheumatoid arthritis was compared in 3 experimental conditions using high performance liquid chromatographic analysis. Major differences were observed when blood and SF neutrophils were incubated with ionophore A23187, the formation of all 5-lipoxygenase products being lower (p less than 0.0005) in the SF neutrophils. Addition of exogenous arachidonic acid to the A23187 stimulated cells partially overcame the difference in 5-lipoxygenase product synthesis between the 2 neutrophil populations. In contrast, upon incubation with arachidonic acid alone, SF neutrophils produced significantly larger amounts of 5-lipoxygenase products. The increased reactivity of the SF neutrophil 5-lipoxygenase to arachidonic acid and the decreased 5-lipoxygenase product synthesis upon A23187 stimulation may be the consequence of the previous activation of the cells and 5-lipoxygenase product synthesis in situ.

Topics: Adult; Aged; Arachidonic Acids; Arthritis, Rheumatoid; Cells, Cultured; Chromatography, High Pressure Liquid; Female; Humans; Lasalocid; Leukotriene A4; Leukotriene B4; Leukotrienes; Male; Middle Aged; Neutrophils; SRS-A; Synovial Fluid