Effect of dihomogammalinolenic acid and its 15-lipoxygenase metabolite on eicosanoid metabolism by human mononuclear leukocytes in vitro: selective inhibition of the 5-lipoxygenase pathway.

The purpose of the present study was to determine the effect of the n-6 fatty acid, dihomogammalinolenic acid (DGLA, 20∶3, n-6) on arachidonic acid (AA) (C20∶4) metabolism by human peripheral mononuclear leukocytes (HPML). After incubation of HPML with A23187 (5 Μ M) and DGLA, the cyclooxygenase (CO) and lipoxygenase (LO) products were separated and quantified by reversed-phase high-performance liquid chromatography (RP-HPLC) combined with radioimmunoassay. DGLA led to no change in PGE formation, but at similar concentrations there was a dose-dependent decrease in LTB formation (IC=45.0 Μ M). The inhibition of LTB formation by DGLA was associated with a dosedependent increase in its 15-LO metabolite 15-hydroxyeicosatrienoic acid (15-HETrE) and its CO metabolite prostaglandin E (PGE). Incubation of HPLM with 15-HETrE (0-1.5 Μ M) alone did not result in a change in PGE formation, whereas 15-HETrE was a much more potent inhibitor of LTB formation (IC=0.5 Μ M) than DGLA. These results show that the addition of DGLA to HPML results in a selective inhibition of LTB formation, presumably via its metabolite (15-HETrE). [ABSTRACT FROM AUTHOR]