Comparison of a recombinant endotoxin-neutralizing protein with a human monoclonal antibody to endotoxin for the treatment of Escherichia coli sepsis in rats

Nathan Kuppermann, Douglas S. Nelson, Richard A. Saladino, Claudette M. Thompson, Felicia Sattler, Thomas J. Novitsky, Gary R. Fleisher, George R. Siber

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

A recombinant endotoxin-neutralizing protein (ENP) from Limulus polyphemus and a monoclonal IgM anti-lipid A antibody (HA-1A) were compared in a rat model of Escherichia coli sepsis. One hour after intraperitoneal challenge with 106 cfu of E. coli O18ac K1, animals were sensitized to endotoxin with lead acetate and treated with ENP, HA-1A, or saline, followed by ceftriaxone and gentamicin. Before treatment, 95% of rats had high-grade bacteremia and high serum endotoxin concentrations, which were similar in all treatment groups (P > .60). One hour after treatment, there was no bacterial growth in any blood sample, and endotoxin concentrations were significantly lower in the ENP group than in the HA-1A and saline groups (P < .01). At 24 h after challenge, survival in the ENP group was significantly higher than in the HA- 1A saline group (P < .001). ENP improved survival in a rat model of E. coli sepsis with high mortality despite effective antibiotic therapy.

Original languageEnglish (US)
Pages (from-to)630-635
Number of pages6
JournalJournal of Infectious Diseases
Volume170
Issue number3
StatePublished - Sep 1994
Externally publishedYes

Fingerprint

Endotoxins
Sepsis
Monoclonal Antibodies
Proteins
Escherichia coli
Horseshoe Crabs
Lipid A
Survival
Ceftriaxone
Escherichia coli endotoxin
Bacteremia
Gentamicins
Anti-Bacterial Agents
Mortality
Antibodies
Growth
Serum

ASJC Scopus subject areas

  • Immunology
  • Public Health, Environmental and Occupational Health

Cite this

Comparison of a recombinant endotoxin-neutralizing protein with a human monoclonal antibody to endotoxin for the treatment of Escherichia coli sepsis in rats. / Kuppermann, Nathan; Nelson, Douglas S.; Saladino, Richard A.; Thompson, Claudette M.; Sattler, Felicia; Novitsky, Thomas J.; Fleisher, Gary R.; Siber, George R.

In: Journal of Infectious Diseases, Vol. 170, No. 3, 09.1994, p. 630-635.

Research output: Contribution to journalArticle

Kuppermann, N, Nelson, DS, Saladino, RA, Thompson, CM, Sattler, F, Novitsky, TJ, Fleisher, GR & Siber, GR 1994, 'Comparison of a recombinant endotoxin-neutralizing protein with a human monoclonal antibody to endotoxin for the treatment of Escherichia coli sepsis in rats', Journal of Infectious Diseases, vol. 170, no. 3, pp. 630-635.
Kuppermann, Nathan ; Nelson, Douglas S. ; Saladino, Richard A. ; Thompson, Claudette M. ; Sattler, Felicia ; Novitsky, Thomas J. ; Fleisher, Gary R. ; Siber, George R. / Comparison of a recombinant endotoxin-neutralizing protein with a human monoclonal antibody to endotoxin for the treatment of Escherichia coli sepsis in rats. In: Journal of Infectious Diseases. 1994 ; Vol. 170, No. 3. pp. 630-635.
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abstract = "A recombinant endotoxin-neutralizing protein (ENP) from Limulus polyphemus and a monoclonal IgM anti-lipid A antibody (HA-1A) were compared in a rat model of Escherichia coli sepsis. One hour after intraperitoneal challenge with 106 cfu of E. coli O18ac K1, animals were sensitized to endotoxin with lead acetate and treated with ENP, HA-1A, or saline, followed by ceftriaxone and gentamicin. Before treatment, 95{\%} of rats had high-grade bacteremia and high serum endotoxin concentrations, which were similar in all treatment groups (P > .60). One hour after treatment, there was no bacterial growth in any blood sample, and endotoxin concentrations were significantly lower in the ENP group than in the HA-1A and saline groups (P < .01). At 24 h after challenge, survival in the ENP group was significantly higher than in the HA- 1A saline group (P < .001). ENP improved survival in a rat model of E. coli sepsis with high mortality despite effective antibiotic therapy.",
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