title: Effects of dietary fish oil on leukocyte leukotriene and PAF generation and on neutrophil chemotaxis.
abstract: The studies of dietary fish oil supplementation in healthy volunteers demonstrate: (1) suppression of PMN LTB4 synthesis after a minimum of 4 weeks of dietary fish oil consumption at a level of 4-6 g omega 3 fatty acids daily; concomitant suppression of the other arachidonate-derived 5-lipoxygenase pathway products and decreased [3H]-arachidonic acid release may be observed under certain conditions, (2) suppression of PMN chemotactic responsiveness to LTB4 and FMLP, (3) delayed kinetics of inhibition of chemotaxis and AA metabolism relative to that of cellular lipid alteration, and (4) dietary EPA is more active than DHA in eliciting these effects. The effects of dietary EPA on monocyte function in healthy volunteers include: (1) suppression of LTB4 synthesis concomitantly with that of the other 5-lipoxygenase pathway products and decreased [3H]-arachidonic acid release, (2) suppression of PAF synthesis, and (3) delayed kinetics of inhibition of PAF generation and AA metabolism relative to that of cellular lipid alteration. The effects of dietary fish oil in RA patients include: (1) decreased arachidonate content of cellular lipids with an augmented EPA content, (2) decreased LTB4 generation by PMN as an isolated effect, indicating inhibition of the epoxide hydrolase enzyme. The decrease in LTB4 generation by PMN correlated with improvement of tender joint count in one study, (3) augmentation of depressed PMN chemotaxis to LTB4 and FMLP, and (4) suppression of monocyte PAF generation. From these studies one may conclude that: (1) omega 3 fatty acids are incorporated into leukocyte cellular phospholipids with a concomitant loss in arachidonic acid, (2) the incorporation of omega 3 fatty acids into leukocyte cellular lipids suppresses two pathways of inflammatory mediator synthesis: the 5-lipoxygenase and the PAF synthesis pathways, (3) receptor-mediated PMN functions are altered by dietary omega 3 fatty acid consumption, and (4) these functional changes may be delayed vis-a-vis changes in cellular lipid composition and may vary with the underlying disease states and/or background medication.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Mass.
authors.forename: R I
authors.initials: RI
authors.lastname: Sperling
mesh_terms: D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D015289:Leukotrienes / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000096:biosynthesis*
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D015289:Leukotrienes; D010972:Platelet Activating Factor