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

• Published in: The Journal of infectious diseases Vol. 179; no. 5; pp. 1278 - 1282
• Main Authors: Suffredini, Anthony F., Hochstein, H. Donald, McMahon, F. Gilbert
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-05-1999; University of Chicago Press; Oxford University Press
• 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; United States; Performance evaluation; Human; Immune response; Intravenous administration; Escherichia coli; Male; Host agent relation; Endotoxin; Biological activity; Dose activity relation; Infection; Toxin; Experimental disease; Bacteriosis; Bacteria; Enterobacteriaceae
• ISSN: 0022-1899; 1537-6613
• 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—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.