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Cachectin: a hormone that triggers acute shock and chronic cachexia.
K J Tracey1, S F Lowry, A Cerami
1Department of Surgery, New York Hospital--Cornell Medical Center, New York 10021-6399.
The Journal of Infectious Diseases
|March 1, 1988
Summary
Septic shock involves cachectin, also known as tumor necrosis factor (TNF). Antibodies against this cytokine protect against lethal infections, indicating its crucial role in sepsis.
Area of Science:
- Immunology
- Pathophysiology
Background:
- Septic shock and invasive infections result from harmful biological substances.
- Identifying these factors led to the discovery of cachectin.
Purpose of the Study:
- To investigate the role of cachectin (tumor necrosis factor) in septic shock and invasive infections.
Main Methods:
- Molecular cloning of cachectin.
- Administration of endotoxin and E. coli to animal models.
- Infusion of TNF in human subjects.
- Measurement of serum cachectin levels in septicemic patients.
Main Results:
- Cachectin is identical to tumor necrosis factor (TNF).
- Cachectin causes shock and organ injury when released into circulation.
- Cachectin antibodies protected against lethal endotoxin and E. coli effects.
- TNF infusion in humans caused fever and hypotension.
- High serum cachectin levels correlated with mortality in meningococcal infections.
Conclusions:
- Cachectin is a key mediator, both necessary and sufficient, for septic shock.
- Chronic cachectin production leads to cachexia and wasting syndromes.
- Cachectin antibodies are a potential therapeutic strategy for infectious diseases.