Blunting the response to endotoxin in healthy subjects: effects of various doses of intravenous fish oil

Pittet, Yann ; Berger, Mette ; Pluess, Thomas-Thi ; Voirol, Pierre ; Revelly, Jean-Pierre ; Tappy, Luc ; Chioléro, René

In: Intensive Care Medicine, 2010, vol. 36, no. 2, p. 289-295

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    Objective: To test the dose response effect of infused fish oil (FO) rich in n-3 PUFAs on the inflammatory response to endotoxin (LPS) and on membrane incorporation of fatty acids in healthy subjects. Design: Prospective, sequential investigation comparing three different FO doses. Subjects: Three groups of male subjects aged 26.8±3.2years (BMI 22.5±2.1). Intervention: One of three FO doses (Omegaven®10%) as a slow infusion before LPS: 0.5g/kg 1day before LPS, 0.2g/kg 1day before, or 0.2g/kg 2h before. Measurements and results: Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-α, stress hormones) were collected. After LPS temperature, ACTH and TNF-α concentrations increased in the three groups: the responses were significantly blunted (p<0.0001) compared with the control group of the Pluess et al. trial. Cortisol was unchanged. Lowest plasma ACTH, TNF-α and temperature AUC values were observed after a single 0.2g/kg dose of FO. EPA incorporation into platelet membranes was dose-dependent. Conclusions: Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effects