Endotoxemia-menace, marker, or mistake?

J Leukoc Biol. 2016 Oct;100(4):687-698. doi: 10.1189/jlb.3RU0316-151R. Epub 2016 Jul 14.


Endotoxemia is in its scientific ascendancy. Never has blood-borne, Gram-negative bacterial endotoxin (LPS) been invoked in the pathogenesis of so many diseases-not only as a trigger for septic shock, once its most cited role, but also as a contributor to atherosclerosis, obesity, chronic fatigue, metabolic syndrome, and many other conditions. Finding elevated plasma endotoxin levels has been essential supporting evidence for each of these links, yet the assays used to detect and quantitate endotoxin have important limitations. This article describes several assays for endotoxin in plasma, reviews what they do and do not measure, and discusses why LPS heterogeneity, LPS trafficking pathways, and host LPS inactivation mechanisms should be considered when interpreting endotoxin assay results.

Keywords: LPS; Limulus; endotoxin; lipopolysaccharide; translocation.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Biological Transport
  • Carboxylic Ester Hydrolases / metabolism
  • Endotoxemia* / blood
  • Endotoxemia* / complications
  • Enzyme-Linked Immunosorbent Assay
  • Gram-Negative Bacteria / chemistry
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Negative Bacterial Infections / blood
  • Gram-Negative Bacterial Infections / complications
  • Humans
  • Intestinal Absorption
  • Limulus Test
  • Lipid A / blood
  • Lipid A / chemistry
  • Lipopolysaccharides / blood
  • Lipopolysaccharides / chemistry
  • Lymph / metabolism
  • Neutralization Tests
  • O Antigens / blood
  • O Antigens / chemistry
  • Structure-Activity Relationship


  • Lipid A
  • Lipopolysaccharides
  • O Antigens
  • Carboxylic Ester Hydrolases
  • acyloxyacyl hydrolase