Neutralization of Endotoxin by a Phospholipid Emulsion in Healthy Volunteers

• Published in: The Journal of infectious diseases Vol. 191; no. 9; pp. 1515 - 1522
• Main Authors: Gordon, Bruce R., Parker, Thomas S., Levine, Daniel M., Feuerbach, Fred, Saal, Stuart D., Sloan, Betty-Jane, Chu, Cindy, Stenzel, Kurt H., Parrillo, Joseph E., Rubin, Albert L.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.05.2005; University of Chicago Press; Oxford University Press
• Subjects: Adult; Bacteria; Biological and medical sciences; Cholesterols; Emulsions; Endotoxins; Endotoxins - adverse effects; Endotoxins - antagonists & inhibitors; Endotoxins - blood; Escherichia coli; Female; Fundamental and applied biological sciences. Psychology; Health care administration; Hemodynamics; Humans; Infectious diseases; Lipids; Lipoproteins; Male; Medical sciences; Microbiology; Phospholipids; Phospholipids - administration & dosage; Phospholipids - blood; Phospholipids - therapeutic use; Placebos; Reference Values; Symptoms; Volunteerism; Infection; Phospholipid; Toxin; Microbiology; Endotoxin; Neutralization
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/428908

BackgroundAn approach to endotoxin (lipopolysaccharide [LPS]) blockade makes use of the ability of lipoproteins, via surface phospholipids, to bind and neutralize LPS. The aim of the present study was to determine whether the intravenous administration of a protein-free, phospholipid-rich emulsion is an effective method for neutralizing the effects of LPS in healthy persons MethodsThis was a double-blind, placebo-controlled study in 20 volunteers. Volunteers received Escherichia coli endotoxin (2 ng/kg) intravenously 2 h into a 6-h infusion of either emulsion (210 mg/kg) or placebo (Intralipid diluted 1:64) ResultsThe volunteers who received emulsion had a lower mean clinical score (P<.01), temperature (P<.05), pulse rate (P<.05), neutrophil count (P<.05), tumor necrosis factor–α level (P<.05), and interleukin-6 level (P<.05) than did the volunteers who received placebo. Response was related to serum phospholipid level. The greatest effects were observed in the volunteers achieving phospholipid levels of ∼500 mg/dL or higher ConclusionPhospholipid emulsion attenuates the clinical and laboratory effects associated with the administration of LPS in humans, suggesting a novel approach to the treatment of endotoxemia