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

Intensive Care Med. 2003 Sep;29(9):1472-81. doi: 10.1007/s00134-003-1900-2. Epub 2003 Jul 25.

Abstract

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.

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

Patients and participants: Ten patients with septic shock and eight healthy controls.

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

Measurements and 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Fat Emulsions, Intravenous / administration & dosage*
  • Fatty Acids, Nonesterified / blood*
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-6 / administration & dosage*
  • Female
  • Fish Oils / administration & dosage
  • Humans
  • Leukotrienes / metabolism
  • Male
  • Middle Aged
  • Neutrophils / metabolism*
  • Phosphatidylinositols / metabolism
  • Pilot Projects
  • Platelet Activating Factor / metabolism
  • Shock, Septic / metabolism
  • Shock, Septic / therapy*
  • Superoxides / metabolism
  • Thromboxanes / metabolism

Substances

  • Fat Emulsions, Intravenous
  • Fatty Acids, Nonesterified
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fish Oils
  • Leukotrienes
  • Phosphatidylinositols
  • Platelet Activating Factor
  • Thromboxanes
  • Superoxides