Cachectin: A Hormone that Triggers Acute Shock and Chronic Cachexia

Septic shock and invasive infection are diseases caused by humoral mediators of both exogenous and endogenous origin. The search for and identification of these factors has led to the discovery and molecular cloning of cachectin. This pyrogenic cytokine is identical to tumor necrosis factor (TNF) and, when released into the circulation, causes profound shock and multiple organ injury. Cachectin antibodies protect against the lethal effects of mice given endotoxin and baboons given E. coli, a result suggesting that this mediator is both necessary and sufficient to provoke septic shock. Cachectin is produced in humans after endotoxin infusion; the infusion of small doses of TNF is associated with fever, rigors, headache, and hypotension. Septicemic patients also produce cachectin, and during meningococcal infection, patients with the highest serum levels of cachectin die. Chronic cachectin production causes a potentially lethal syndrome of cachexia, anemia, and protein and lipid wasting. Future investigation is being directed toward the development of cachectin antibodies for use in treating the humorally mediated systemic complications of infectious disease.