Metabolism of eicosapentaenoic acid (EPA) and effect of EPA on arachidonic acid (AA) metabolism in human blood monocytes in vitro were examined. Highly purified monocytes were preparated by an improved method in which hypertonic treatment was employed. Metabolism of EPA in monocytes stimulated with calcium ionophore A 23187 was studied compared with that of AA. 5-lipoxygenase (5-LO) metabolites of AA or EPA were separated and quantitated by reverse phase-HPLC (RP-HPLC) . Production of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE), AA derived metabolites, were inhibited and formation of LTB5 and 5-hydroxyeicosapentaenoic acid (5-HEPE), EPA derived metabolites, were increased dose dependently by the addition of exogenous EPA (1.0-5.0μg/ml) in A 23187 stimulated monocytes.
The current data indicate that EPA is a good substrate for 5-LO and is metabolized to LTB5 by A 23187 stimulation and also inhibits production of LTB4 in monocytes. It is well known that monocytes play an important role in inflammation and immune response, so that EPA might exert its antiinflammatory or immunomodulatory effect through the modulation of production of 5-LO metabolites especially LTB4 and LTB5 in monocytes.
