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


METHODS
Prospective, sequential investigation comparing three different FO doses.


METHODS
Three groups of male subjects aged 26.8 +/- 3.2 years (BMI 22.5 +/- 2.1).


METHODS
One of three FO doses (Omegaven10%) 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.


RESULTS
Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-alpha, stress hormones) were collected. After LPS temperature, ACTH and TNF-alpha 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-alpha and temperature AUC values were observed after a single 0.2 g/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 0.2 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.
Pittet
Yann K
YK
Service of Adult Intensive Care Medicine and Burns Centre, CHUV, 1011 Lausanne, Switzerland.
Berger
Mette M
MM
Pluess
Thomas-Thi
TT
Voirol
Pierre
P
Revelly
Jean-Pierre
JP
Tappy
Luc
L
Chioléro
René L
RL
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000328:Adult; D002153:Calorimetry, Indirect; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011446:Prospective Studies; D018805:Sepsis / Q000378:metabolism* / Q000628:therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D004731:Endotoxins; D005395:Fish Oils; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone