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The systemic inflammatory response: perspective of human endotoxemia
1Department of Surgery, Harvard University, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Shock (Augusta, Ga.)
|January 1, 1996
Summary
Human endotoxemia studies are safe and reveal that therapies effective in animals fail in humans. This model can screen anti-mediator treatments for clinical trials.
Area of Science:
- Immunology
- Pharmacology
- Clinical Medicine
Background:
- Advances in detecting cytokines have spurred research into endotoxin's role in initiating inflammatory mediators.
- Endotoxin administration in humans is a model to study inflammatory responses and test therapies.
Purpose of the Study:
- To review studies of endotoxin administration in healthy humans.
- To collate data on mediator elaboration and therapies targeting them.
- To evaluate the safety and efficacy of human endotoxemia models for therapy screening.
Main Methods:
- Systematic review of over 60 studies involving endotoxin administration (Escherichia coli) in healthy humans.
- Analysis of data from endotoxin administration alone and with various pretreatments (antiendotoxin, receptor antagonists, anti-inflammatory agents).
- Monitoring of endpoints including vital signs, blood cell counts, coagulation, hormone secretion, and cytokine levels.
Main Results:
- Human endotoxemia trials are safe.
- Pretreatments that succeed in animal models show limited success in human endotoxemia.
- Therapeutic outcomes in human endotoxemia mirror those of anti-mediator therapy in Gram-negative bacteremia.
Conclusions:
- Human endotoxemia models are safe and can be used to screen potential therapies.
- Therapies successful in animal models do not always translate to efficacy in humans.
- This model offers a valuable platform for identifying anti-mediator treatments for further clinical trials.