Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody.
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.
Taylor
F B
FB
Oklahoma Medical Research Foundation, Oklahoma City.
Chang
A
A
Ruf
W
W
Morrissey
J H
JH
Hinshaw
L
L
Catlett
R
R
Blick
K
K
Edgington
T S
TS
D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001794:Blood Pressure; D003404:Creatinine / Q000378:metabolism; D004927:Escherichia coli Infections / Q000473:pathology; D005167:Factor VII / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D010215:Papio; D012772:Shock, Septic / Q000517:prevention & control*; D013154:Spleen / Q000473:pathology; D013925:Thromboplastin / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005167:Factor VII; D005340:Fibrinogen; D013925:Thromboplastin; D003404:Creatinine