Dietary fish oil enhances macrophage production of nitric oxide.
Nitric oxide (NO) is recognized as an important mediator of hemodynamic regulation and multisystem organ failure (MOF). Although polyunsaturated fatty acids (PUFA) are known to modify the elaboration of some humoral mediators in MOF, their effect upon NO production has not been evaluated. This study was designed to examine the effect of omega-3 (omega 3) and omega-6 (omega 6) PUFA on macrophage production of NO, TNF, PGE2, and PGI2. Rats were fed diets of 18% by calorie safflower oil (omega 6) or fish oil (omega 3) for 12 days. Bronchoalveolar macrophages (BAM) were divided into group A (medium only), group B (0.5 microgram/ml PGE2 or PGI2 + medium) or group C (10 microM indomethacin+medium). Cells were stimulated with 100 U/ml interferon-gamma and 10 micrograms/ml Escherichia coli-LPS. In group A, BAM from animals fed omega 3 produced significantly more NO (3.64 vs 1.92 microM, P < 0.05) and TNF (8.52 vs 1.75 micrograms/ml, P < 0.05) than BAM from omega 6-fed animals. The addition of exogenous PGE2 or PGI2 (group B) ablated the difference in NO and TNF observed in group A. Indomethacin also (group C) ablated the difference in NO and TNF production seen in omega 3- and omega 6-fed animals noted in group A. These data demonstrate that PUFA influence BAM production of NO and TNF. Changes in the omega 6-derived prostanoids may account for the differences in TNF production, but these data suggest that PGE2 and PGI2 are not responsible for the observed differences in NO production.(ABSTRACT TRUNCATED AT 250 WORDS)
Chaet
M S
MS
Department of Surgery, Children's Hospital Research Foundation, University of Cincinnati, Ohio 45229.
Garcia
V F
VF
Arya
G
G
Ziegler
M M
MM
D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin