Publication | Closed Access
Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody.
443
Citations
0
References
1991
Year
Microbial PathogensImmunologyLd100 Escherichia ColiBacterial PathogensInflammationSepsisInfection ControlImmune MediatorMonoclonal AntibodyVirulence FactorImmunoglobulin GDisease BiologyTissue FactorClinical MicrobiologyEssential MediatorsCytokineImmune Effector FunctionsMucosal ImmunologyPathogenesisMedicine
Gram‑negative bacteremia, driven by LPS, TNF, and IL‑1, commonly leads to lethal septic shock and induces a coagulopathy through tissue factor expression on macrophages and endothelial cells. Pretreatment with 500 µg/kg of an anti‑tissue‑factor monoclonal antibody, either IgG or Fab, reduced coagulopathy and protected baboons from lethal E.
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 micrograms/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.