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Factor XII activation and inhibition in inflammation
1Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140.
Agents and Actions. Supplements
|January 1, 1993
Summary
Activation of the kallikrein-kinin system contributes to hypotension in sepsis. Inhibiting this system, particularly bradykinin, can prevent severe hypotension and improve survival in septic shock.
Area of Science:
- Biochemistry
- Physiology
- Immunology
Background:
- Sepsis involves complex biochemical pathways, including the kallikrein-kinin system.
- Activation of proteases in this system is observed during septic shock and acute respiratory distress.
Purpose of the Study:
- To investigate the role of the kallikrein-kinin system in sepsis-induced hypotension.
- To evaluate the therapeutic potential of inhibiting this system.
Main Methods:
- Functional and immunological assays were used to measure system components.
- Animal models of septicemia were employed to test protease inhibitors and monoclonal antibodies.
- Cardiopulmonary bypass models were used to study elastase release.
Main Results:
- Protease activation and kininogen decrease were observed during sepsis.
- Inhibitors and antibodies targeting the contact system prevented kallikrein formation and hypotension.
- Bradykinin was identified as a key mediator of hypotension.
- Kallikrein activation in cardiopulmonary bypass led to neutrophil degranulation and elastase release.
Conclusions:
- The kallikrein-kinin system, particularly bradykinin, plays a significant role in sepsis-induced hypotension.
- Inhibition of this system offers a potential therapeutic strategy for improving outcomes in sepsis.
- Kallikrein inhibition also mitigates elastase release during cardiopulmonary bypass.