Eicosapentaenoic acid modulates arachidonic acid metabolism in rat alveolar macrophages.

Eicosapentaenoic acid (EPA) is an unsaturated fatty acid contained in fish oils. In order to clarify the mechanism of its anti-inflammatory effects on the lung, we studied arachidonic acid (AA) metabolism by in vitro exposure of rat alveolar macrophages to EPA. EPA was found to inhibit the endogenous production of leukotriene B4 (LTB4) from AA. At a low concentration of EPA, generation of LTB5 was increased, while at a high concentration it was decreased. These results suggest that at a lower concentration EPA may be competitive with AA as a substrate, and that at a higher concentration it may directly inhibit AA metabolism via inhibition of 5-lipoxygenase or phospholipase A2.