Dose-Related Inflammatory Effects of Intravenous Endotoxin in Humans: Evaluation of a New Clinical Lot of Escherichia coli O:113 Endotoxin

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...

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Bibliographic Details
Published in:The Journal of infectious diseases 1999-05, Vol.179 (5), p.1278-1282
Main Authors: Suffredini, Anthony F., Hochstein, H. Donald, McMahon, F. Gilbert
Format: Article
Language:English
Subjects:
Adult
Bacterial diseases
Biological and medical sciences
Concise Communications
Cytokines
Cytokines - blood
Dosage
Dose response relationship
Dose-Response Relationship, Drug
Endotoxins
Endotoxins - administration & dosage
Endotoxins - toxicity
Escherichia coli
Evaluation Studies as Topic
Experimental bacterial diseases and models
Health care administration
Humans
Hydrocortisone - blood
Infectious diseases
Inflammation - immunology
Inflammation - pathology
Injections, Intravenous
Leukocyte Count
Leukocytes
Male
Medical sciences
Medication administration
Middle Aged
National Institutes of Health (U.S.)
Neutrophils
Placebos
Reference Standards
United States
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Summary: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—α (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.
ISSN:0022-1899
1537-6613
DOI:10.1086/314717