Conversion of endogenous arachidonic acid to 5,15-diHETE and lipoxins by polymorphonuclear cells from patients with rheumatoid arthritis

Abstract

The conversion of endogenous arachidonic acid (AA) by polymorphonuclear cells (PMN) from patients with rheumatoid arthritis (RA) was studied before (D0) and one day (D1) after antiinflammatory drug therapy. The biosynthesis of 5,15-diHETE and lipoxins (LXS), were investigated ex vivo, after PMN stimulation by ionophore A23187 without exogenous addition of 15-HETE. The eicosanoids were resolved by RP-HPLC and simultaneously detected at 246 and 302 nm respectively. Large amounts of 5,15-diHETE (50 to 400 ng/10(7) PMN) and significant levels of LXS (from 2 to 20 ng/10(7) PMN) were produced with individual differences between donors. Metabolite levels varied between patients but this work showed for the first time a linear relationship between the amounts of 5,15-diHETE and LXS. Moreover LXS production after treatment may be related to long-term clinical improvement of patients.