LONG-CHAIN PREDOMINANT LIPID EMULSIONS INHIBIT IN-VITRO MACROPHAGE TUMOR-NECROSIS-FACTOR PRODUCTION

Intravenous lipid emulsions are an important component of parenteral nutrition. Despite their benefits, lipid emulsions have been associated with higher rates of bacteremia in neonates. Therefore we investigated the effect of lipid emulsions on the inflammatory response by examining their effect on in vitro macrophage tumor necrosis factor (TNF) production of two distinct macrophage populations. Through the use of endotoxin-free phosphate buffered saline, peritoneal (PER) and alveolar (ALV) macrophages were isolated from male Sprague-Dawley rats (weighing 125 to 150 g) with endotoxin-free phosphate buffered saline. Cell counts were adjusted to 2 x 10(6) cells/mL in RPMI with 2% fetal calf serum. Three hundred microliters of the cells were incubated in a 24-well culture dish with media or media with intralipid (100 mug/dL) for 16 hours. After washing each well three times, the cells were stimulated for 2 or 16 hours with Escherichia coli lipopolysaccharide (150 muL of 1 mug/mL). The supernatants were assayed for TNF using the WEHI 164:13 bioassay and TNF levels were expressed as picograms per milliliter. Student's unpaired t test was used for data analysis. Lipid-exposed PER and ALV macrophages in vitro TNF levels were significantly lower after 2 hours (12,591 pg/mL +/- 3837 vs 20,591 pg/mL +/- 6344 for PER, 3894 pg/mL +/- 1258 vs 13,177 pg/mL +/- 3266 for ALV) and 16 hours (6427 pg/mL +/- 3050 vs 12,353 pg/mL +/- 4877 for PER; 131,6000 pg/mL +/- 7317 vs 354,680 pg/mL +/-31,605 for ALV) of endotoxin stimulation. TNF production seems to be impaired in macrophages exposed to a .1% lipid emulsion for 16 hours. By impairing TNF production, lipid emulsions may mitigate an important proximal mediator of the immune response.