Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation.
OBJECTIVE
To compare the effects of a conventional omega-6 lipid infusion and a fish oil based (omega-3) lipid infusion for parenteral nutrition on neutrophil function, lipid mediators, and plasma free fatty acids.


METHODS
Open-label, randomized, pilot study in a university hospital medical intensive care unit and experimental laboratory.


METHODS
Ten patients with septic shock and eight healthy controls.


METHODS
Patients (five per group) requiring parenteral nutrition received intravenously either a omega-3 or a omega-6 lipid emulsion for a 10-day period.


RESULTS
At baseline levels of plasma free fatty acids were elevated several-fold, including high concentrations of the omega-6 lipid precursor arachidonic acid (AA). Neutrophils isolated from septic patients displayed markedly reduced responsiveness to ex vivo stimulation, including lipid mediator generation [leukotrienes (LT), PAF], respiratory burst, and phosphoinositide hydrolysis signaling. Under the omega-6 lipid infusion regimen abnormalities in plasma free fatty acids and impairment of neutrophil functions persisted or worsened. In contrast, a rapid switch in the plasma free fatty acid fraction to predominance of the omega-3 acids eicosapentaenoic acid and docosahexaenoic acid over AA occurred in response to omega-3 lipid infusion. LTB(5), in addition to LTB(4), appeared upon neutrophil stimulation originating from these patients, and neutrophil function was significantly improved in the omega-3 lipid group.


CONCLUSIONS
omega-3 vs. omega-6 lipid emulsions differentially influence the plasma free fatty acid profile with impact on neutrophil functions. Lipid-based parenteral nutrition in septic patients may thus exert profound influence on sequelae and status of immunocompetence and inflammation.
Mayer
Konstantin
K
Department of Internal Medicine, Justus Liebig University, Klinikstrasse 36, Giessen, Germany. Konstantin.Mayer@innere.med.uni-giessen.de
Fegbeutel
Christine
C
Hattar
Katja
K
Sibelius
Ulf
U
Krämer
Hans-Joachim
HJ
Heuer
Kai-Uwe
KU
Temmesfeld-Wollbrück
Bettina
B
Gokorsch
Stephanie
S
Grimminger
Friedrich
F
Seeger
Werner
W
D000328:Adult; D000368:Aged; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010865:Pilot Projects; D010972:Platelet Activating Factor / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism / Q000628:therapy*; D013481:Superoxides / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism
D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D015289:Leukotrienes; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D013931:Thromboxanes; D013481:Superoxides