Interactions between fatty acids and arginine metabolism: Implications for the design of immune-enhancing diets

Background: Trauma increases the enzyme arginase, thus depleting arginine necessary for producing nitric oxide. Arginine and omega-3 fatty acids are components in immune-enhancing diets. These diets decrease infections in surgical patients, perhaps by preventing arginine deficiency. This study examines whether w-3 fatty acids alter the metabolic fate of arginine. Thus, we hypothesized there could be differential effects of varying prostaglandins on regulation of arginase. Methods: Prostaglandins PGE1, PGE2, and PGE3 were tested using RAW 264.7 cells cultured in the presence of these prostaglandins for 24 hours. IL-13 (10 ng/mL) was added 24 hours later to induce arginase I. NO production was induced by adding LPS (2 mug/mL) to the cultures after another 24 hours. Results: Arginase activity (nmol/min/mg) was induced by all prostaglandins but significantly more by PGE1 (466.05 +/- 30.25) and PGE2 (248.45 +/- 15.05) than PGE3 (139.87 +/- 19.88; P < .002) when co-cultured with IL-13. Western blots correlated the increase in arginase I expression. Nitrate levels (muM) were inversely proportional to activity with PGE3 having the highest production (3.89 +/- 0.19) and PGE2 and PGE1 with the lowest (2.75 +/- 0.49 and 1.54 +/- 0.19, respectively). Inhibition of arginase I using nor-hydroxyarginine increased and equalized nitrate levels. Conclusions: Different prostaglandins significantly alter the metabolism of arginine. Prostaglandins from omega-6 fatty acids increases arginase I expression. By decreasing arginase I expression, prostaglandins from omega-3 fatty acids may increase available arginine. The specific combinations of dietary fatty acids and arginine should be considered when tailoring dietary regimens.