DIETARY FISH-OIL ENHANCES MACROPHAGE PRODUCTION OF NITRIC-OXIDE

Nitric oxide (NO) is recognized as an important mediator of hemodynami c regulation and multisystem organ failure (MOF). Although polyunsatur ated fatty acids (PUFA) are known to modify the elaboration of some hu moral mediators in MOF, their effect upon NO production has not been e valuated. This study was designed to examine the effect of omega-3 (om ega 3) and omega-6 (omega 6) PUPA on macrophage production of NO, TNF, PGE(2), and PGI(2). Rats were fed diets of 18% by calorie safflower o il (omega 6) or fish oil (omega 3) for 12 days. Bronchoalveolar macrop hages (BAM) were divided into group A (medium only), group B (0.5 mu g /ml PGE(2) or PGI(2) + medium) or group C (10 mu M indomethacin + medi um). Cells were stimulated with 100 U/ml interferon-gamma and 10 mu g/ ml Escherichia coli-LPS. In group A, BAM from animals fed omega 3 prod uced significantly more NO (3.64 vs 1.92 mu M, P < 0.05) and TNF (8.52 vs 1.75 mu g/ml, P < 0.05) than BAM from omega 6-fed animals. The add ition of exogenous PGE(2) or PGI(2) (group B) ablated the difference i n 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-f ed animals noted in group A. These data demonstrate that PUFA influenc e BAM production of NO and TNF. Changes in the omega 6-derived prostan oids may account for the differences in TNF production, but these data suggest that PGE(2) and PGI(2) are not responsible for the observed d ifferences in NO production. Through its effect upon macrophage NO pro duction, manipulation of exogenous omega 3/omega 6 PUFA may be of valu e in the management of patients at risk for development of MOF. (C) 19 94 Academic Press, Inc.