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

Abstract

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.

• Authors: A F Suffredini, H D Hochstein, F G McMahon
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 179 Issue 5 Pg. 1278-82 (May 1999) ISSN: 0022-1899 [Print] United States
• PMID: 10191237 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Endotoxins
• endotoxin, Escherichia coli
• Hydrocortisone

Topics

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