Effect of short-term enteral feeding with eicosapentaenoic and gamma-linolenic acids on alveolar macrophage eicosanoid synthesis and bactericidal function in rats

Objectives: Because vasoactive eicosanoids derived from arachidonic acid pr esent in immune cell phospholipids promote lung inflammation in critically ill patients, novel experimental diets containing eicosapentaenoic acid fro m fish oil and gamma-linolenic acid from borage oil have been designed to l imit arachidonic acid metabolism. However, excess dietary eicosapentaenoic acid impairs superoxide formation and bacterial killing by immune cells. Th e present study determined whether short-term enteral feeding with diets en riched with either eicosapentaenoic acid alone or in combination with gamma -linolenic acid would modulate alveolar macrophage eicosanoid synthesis wit hout compromising bactericidal function. Design: Prospective, randomized, controlled, blinded study. Setting: University medical center. Subjects.. Adult male Sprague-Dawley rats. Interventions: Rats underwent surgical placement of a gastroduodenal feedin g catheter and were randomly assigned to receive one of three high-fat (55. 2% of total calories), low-carbohydrate diets containing isocaloric amounts of lipids for 4 days. The control diet was enriched with linoleic acid, wh ereas the two test diets were low in linoleic acid and enriched with either 5 mole % eicosapentaenoic acid alone or in combination with 5 mole % gamma -linolenic acid. Alveolar macrophages were then procured to assess phosphol ipid fatty acid composition, eicosanoid synthesis after stimulation with en dotoxin, superoxide formation and phagocytosis by flow cytometry, and killi ng of Staphylococcus aureus. Measurements and Main Results: Alveolar macrophage levels of arachidonic ac id were significantly (p < .01) lower and levels of eicosapentaenoic and di homo-gamma-linolenic acids were higher after feeding the eicosapentaenoic a nd gamma-linolenic acid diet vs. the linoleic acid diet. Ratios of thrombox ane B-2,/B-3, leukotriene B-4/B-5, and prostaglandin E-2/E-1 were reduced i n the macrophages from rats given either the eicosapentaenoic acid or eicos apentaenoic acid with gamma-linolenic acid diet compared with ratios from r ats given the linoleic acid diet. Macrophages from rats given the eicosapen taenoic with y-linolenic acid diet released 35% or 24% more prostaglandin E -1 than macrophages from rats given either the linoleic acid or the eicosap entaenoic acid diet, respectively. Macrophage superoxide generation, phagoc ytosis of opsonized zymosan, and killing of S. aureus were similar irrespec tive of dietary treatment. Conclusion: Short-term enteral feeding with an eicosapentaenoic acid-enrich ed or eicosapentaenoic with gamma-linolenic acid-enriched diet rapidly modu lated the fatty acid composition of alveolar macrophage phospholipids, prom oted a shift toward formation of less inflammatory eicosanoids by stimulate d macrophages, but did not impair alveolar macrophage bactericidal function relative to responses observed after feeding a linoleic acid diet.