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Background: enteral supply of ?-3 polyunsaturated fatty acids has been used in an attempt to modulate inflammation and improve outcome in critically ill patients. However, enteral administration may be slow to change membrane composition and therefore may not be the best route to supply these fatty acids in patients with acute conditions. This study evaluated the effects of short-term intravenous (IV) administration of fish oil–based lipid emulsion (FLE) as pharmaconutrition on cytokine levels in critically ill elderly patients. Methods: enterally fed patients (n = 40; aged 60–80 years) were recruited in the first 48 hours of intensive care unit (ICU) admission. Fifteen patients received IV FLE (0.2 g/kg body weight) over 6 hours for 3 consecutive days, and 25 patients did not receive IV lipid (control). Samples were collected before and 24 hours and 72 hours after the third FLE infusion. Nutrient intakes, clinical parameters, and serum cytokine concentrations were measured. Results: compared with the control, FLE resulted in higher energy intake, lower serum tumor necrosis factor–? and interleukin (IL)–8 concentrations, and higher serum IL-10. These differences occurred around 7–9 days of ICU stay at the time of the patient’s extubation. ICU stay, mortality, and markers of coagulation and liver function did not differ between groups. Conclusions: short-term IV FLE modulates some inflammatory markers in critically ill elderly patients receiving enteral nutrition (EN), suggesting an anti-inflammatory effect. This may be a benefit and suggests a role for FLE administration as a supplement in elderly ICU patients receiving standard EN