Dose-related inflammatory effects of intravenous endotoxin in humans: evaluation of a new clinical lot of Escherichia coli O:113 endotoxin

J Infect Dis. 1999 May;179(5):1278-82. doi: 10.1086/314717.


The administration of reference endotoxin (Escherichia coli O:113, Lot EC-5) to humans has been an important means to study inflammation in vivo; however, the supply of Lot EC-5 is depleted. A new lot of reference endotoxin (Clinical Center reference endotoxin [CCRE]), derived from the original bulk material extracted from E. coli O:113, was processed. The effects of 0-, 1-, 2-, and 4-ng/kg doses of intravenous CCRE and EC-5 were studied in 20 male subjects. CCRE resulted in dose-related increases in symptoms, temperature (P=. 016), total leukocyte count (P=.014), tumor necrosis factor-alpha (P=.004), interleukin (IL)-1 receptor antagonist (P=.004), IL-6 (P=. 005), IL-8 (P=.011), cortisol (P<.05), and C-reactive protein (P=. 04). These responses were attenuated (all P<.012) in subjects given Lot EC-5 (4 ng/kg) in comparison with those in subjects given CCRE, showing that, over several years, EC-5 had lost potency. Thus, in healthy subjects, the magnitude of exposure to CCRE results in a graded dose response of major components of innate immunity.

MeSH terms

  • Adult
  • Cytokines / blood
  • Dose-Response Relationship, Drug
  • Endotoxins / administration & dosage*
  • Endotoxins / toxicity
  • Evaluation Studies as Topic
  • Humans
  • Hydrocortisone / blood
  • Inflammation / immunology*
  • Inflammation / pathology*
  • Injections, Intravenous
  • Leukocyte Count
  • Male
  • Middle Aged
  • National Institutes of Health (U.S.)
  • Reference Standards
  • United States


  • Cytokines
  • Endotoxins
  • endotoxin, Escherichia coli
  • Hydrocortisone