Dietary n-3 fatty acids accelerate catabolism of leukotriene B4 in human granulocytes.
Addition of n-3 fatty acids to a human diet for more than 3 weeks lowers levels of the powerful proinflammatory compound, leukotriene (LT) B4. 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 LTB4, 20-OH-LTB4, 20-COOH-LTB4 as well as LTB5, 20-OH-LTB5 and 20-COOH-LTB5 were measured by high-pressure liquid chromatography (HPLC) after stimulation and extraction of a platelet-free granulocyte preparation (92% neutrophils). LTB5 and 20-COOH-LTB5 were only detected during n-3 fatty acids, when 20-OH-LTB5 increased from trace amounts to substantial quantities. Importantly, levels of catabolites of LTB4, i.e., 20-OH-LTB4 and 20-COOH-LTB4 were not significantly altered throughout the study. However, the level of LTB4 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 LTB4 are lowered by a combination of accelerated catabolism and diminished LTB4 generation. This newly observed mechanism of increased LT catabolism may be mediated via induction of peroxisomal enzymes catabolizing leukotrienes B.
von Schacky
C
C
Medizinische Klinik, University of Munich, Germany.
Kiefl
R
R
Marcus
A J
AJ
Broekman
M J
MJ
Kaminski
W E
WE
D000328:Adult; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D013997:Time Factors
D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D007975:Leukotriene B4