Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody

F. B. Taylor, A. Chang, W. Ruf, J. H. Morrissey, L. Hinshaw, R. Catlett, K. Blick, T. S. Edgington

Research output: Contribution to journalArticlepeer-review

Abstract

Gram-negative bacteremia poses a major health problem, causing one-half of cases of lethal septic shock acquired during hospitalization. Bacterial lipopolysaccharide (LPS) and the inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), have been shown to be essential mediators of septic shock. Among the effects of these mediators is a coagulopathy that may be triggered by induced expression of tissue factor (TF) on macrophages and endothelial cells. We now report that 500 μg/kg of either immunoglobulin G (IgG) or Fab fragments of a monoclonal antibody against TF administered to baboons as a pretreatment attenuates the coagulopathy and protects against LD100 Escherichia coli. This study provides direct evidence of an essential effector role for TF in septic shock.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalCirculatory Shock
Volume33
Issue number3
StatePublished - 1991

Keywords

  • baboons
  • cardiovascular shock
  • cell injury
  • disseminated intravascular coagulation (DIC)
  • gram-negative bacteremia
  • inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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