Dietary n − 3 fatty acids accelerate catabolism of leukotriene B 4 in human granulocytes

Abstract

Addition of n − 3 fatty acids to a human diet for more than 3 weeks lowers levels of the powerful proinflammatory compound, leukotriene (LT) B 4. This can be shown ex vivo after stimulation of human granulocytes with ionophore A23187. In a controlled, randomized, observer-blind study in 14 human volunteers, we investigated the effect of adding 7 g/day of a 85% n − 3 fatty acid concentrate to the diet of 7 volunteers (7 served as controls). Levels of LTB 4, 20-OH-LTB 4, 20-COOH-LTB 4 as well as LTB 5, 20-OH-LTB 5 and 20-COOH-LTB 5 were measured by high-pressure liquid chromatography (HPLC) after stimulation and extraction of a platelet-free granulocyte preparation (92% neutrophils). LTB 5 and 20-COOH-LTB 5 were only detected during n − 3 fatty acids, when 20-OH-LTB 5 increased from trace amounts to substantial quantities. Importantly, levels of catabolites of LTB 4, i.e., 20-OH-LTB 4 and 20-COOH-LTB 4 were not significantly altered throughout the study. However, the level of LTB 4 itself was reduced dramatically after 6 weeks (less so after 1 week) of dietary n − 3 fatty acid administration. These data demonstrate that during dietary n − 3 fatty acids levels of LTB 4 are lowered by a combination of accelerated catabolism and diminished LTB 4 generation. This newly observed mechanism of increased LT catabolism may be mediated via induction of peroxisomal enzymes catabolizing leukotrienes B.