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.
Medizinische Klinik, University of Munich, Germany.
C
C
von Schacky
R
R
Kiefl
A J
AJ
Marcus
M J
MJ
Broekman
W E
WE
Kaminski
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