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Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody
1Oklahoma Medical Research Foundation, Oklahoma City.
Circulatory Shock
|March 1, 1991
Summary
This study shows that blocking tissue factor (TF) with an antibody in baboons prevents coagulopathy and protects against lethal E. coli infection, highlighting TF's role in septic shock.
Area of Science:
- Immunology
- Pathophysiology
- Microbiology
Background:
- Gram-negative bacteremia is a leading cause of lethal hospital-acquired septic shock.
- Bacterial lipopolysaccharide (LPS), TNF, and IL-1 are key mediators of septic shock.
- Septic shock involves coagulopathy, potentially triggered by tissue factor (TF) induction.
Purpose of the Study:
- To investigate the role of tissue factor (TF) in the pathogenesis of septic shock.
- To evaluate the therapeutic potential of anti-TF antibodies in a baboon model of Gram-negative bacteremia.
Main Methods:
- Baboons were pretreated with immunoglobulin G (IgG) or Fab fragments of a monoclonal antibody against TF.
- Animals were challenged with a lethal dose (LD100) of Escherichia coli.
- Coagulopathy and survival rates were assessed.
Main Results:
- Pretreatment with anti-TF IgG or Fab fragments significantly attenuated coagulopathy.
- Monoclonal antibody treatment protected baboons against lethal E. coli challenge.
- This demonstrates TF's essential role in mediating septic shock.
Conclusions:
- Tissue factor (TF) is a critical mediator in the development of septic shock.
- Targeting TF with antibodies offers a potential therapeutic strategy for septic shock.
- Further research into anti-TF therapies for sepsis is warranted.