Blunting the response to endotoxin in healthy subjects: effects of various doses of intravenous fish oil
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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.
Prospective, sequential investigation comparing three different FO doses.
Three groups of male subjects aged 26.8 ± 3.2 years (BMI 22.5 ± 2.1).
One of three FO doses (Omegaven®10%) as a slow infusion before LPS: 0.5 g/kg 1 day before LPS, 0.2 g/kg 1 day before, or 0.2 g/kg 2 h 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 0.2 g/kg dose of FO. EPA incorporation into platelet membranes was dose-dependent.
Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2 g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effects.
KeywordsInflammation Sepsis PUFA Downregulation
We are grateful to Prof. Yvon Carpentier and his team (NUTRISUB Laboratory ULB, Brussels, Belgium) for the determinations of the fatty acid membrane incorporation and to Dr. Christiane Ruffieux and Pierre Bady (Institute of Social and Preventive Medicine, University of Lausanne) for statistical advice. The study was primarily supported by a grant from the Swiss National Science Foundation (no. 32-61582.00) and completed by a partial grant from Fresenius Kabi AG (Bad Homburg, Germany) for laboratory determinations.
Conflict of interest statement
None of the authors has any conflict of interest, such as bonds, or any economic implications in the industry. R.L. Chiolero and M.M. Berger deliver invited lectures for Fresenius Kabi AG, B. Braun and Nestlé. The groups research is partially supported by grants from Fresenius Kabi AG and B. Braun.
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