DIETARY FISH-OIL AND FISH AND BORAGE OIL SUPPRESS INTRAPULMONARY PROINFLAMMATORY EICOSANOID BIOSYNTHESIS AND ATTENUATE PULMONARY NEUTROPHILACCUMULATION IN ENDOTOXIC RATS

Objective: Proinflammatory eicosanoids and cytokines are important med iators of local inflammation in acute lung injury. We determined ii en teral nutrition with anti-inflammatory fatty acids, eicosapentaenoic a cid, and gamma-linolenic acid would reduce the intrapulmonary synthesi s of proinflammatory eicosanoids and cytokines and pulmonary neutrophi l accumulation in a rat model of acute lung injury. Design: Prospectiv e, randomized, controlled, double-blind study. Setting: Research labor atory at a university medical center. Subjects: Male Long-Evans rats ( 250 g). Interventions: Rats were randomly assigned to three dietary tr eatment groups and fed nutritionally complete diets (300 kcal/kg/day) containing 55.2% of the total calories from fat with either 97% corn o il, 20% fish oil, or 20% fish and 20% borage oil for 21 days. On day 2 2, bronchoalveolar lavage was performed 2 hrs after an intravenous inj ection of Salmonella enteritidis endotoxin (10 mg/kg) or saline. Bronc hoalveolar ravage fluid was analyzed for leukotriene B-4, leukotriene C-4/D-4, thromboxane B-2, prostaglandin E-2, 6 keto-prostaglandin F-1 alpha, tumor necrosis factor (TNF)-alpha, and macrophage inflammatory protein-2 (MIP-2). Lung myeloperoxidase activity (a marker for neutrop hil accumulation) and phospholipid fatty acid composition were also de termined. Measurements and Main Results: Lung phospholipid concentrati ons of arachidonic acid were lower and the concentrations of eicosapen taenoic acid and docosahexaenoic acid were higher with fish oil and fi sh and borage oil as compared with corn oil. Dihomo-gamma-linolenic ac id, the desaturated and elongated intermediate of gamma-linolenic acid , increased with fish and borage oil as compared with fish oil and cor n oil. The levels of leukotriene B-4, leukotriene C-4/D-4, 6-keto-pros taglandin F-1 alpha and thromboxane B-2 with corn oil were significant ly increased with endotoxin as compared with saline. In contrast to th e corn oil group, endotoxin did not significantly increase bronchoalve olar lavage levels of leukotriene B-4, leukotriene C-4/D-4, and thromb oxane B-2 above those of saline-treated rats with fish oil and fish an d borage oil. Lung myeloperoxidase activity was significantly increase d in endotoxin-treated rats compared with those rats given saline in a ll dietary treatment groups. However, lung myeloperoxidase activity wa s significantly lower with either fish oil or fish and borage oil as c ompared with corn oil after endotoxin. Although endotoxin increased th e levels of TNF-alpha and MIP-2 with all dietary treatment groups as c ompared with saline-treated rats, there were no significant difference s in the levels of either cytokine between the dietary treatment group s. Conclusions: These results indicate that dietary fish oil and fish and borage oil as compared with corn oil may ameliorate endotoxin-indu ced acute lung injury by suppressing the levels of proinflammatory eic osanoids;(but not TNF-alpha or MIP-2) in bronchoalveolar lavage fluid and reducing pulmonary neutrophil accumulation.