Studies of cachexia in parasitic infection.

Cachexia and septic shock, syndromes associated with chronic and acute infection, respectively, are mediated by endogenous factors. The search for humoral mediators of cachexia led to the isolation of the cytokine known as cachectin/TNF. A biologic role for cachectin/TNF in cachexia has been identified: it induces a catabolic state in adipose and skeletal muscle cells in vitro, and animals persistently exposed to it in vivo become cachectic. Cachectin/TNF was also discovered to be a primary, essential mediator of septic shock. The acute administration of the recombinant protein causes shock, tissue injury, and derangements of metabolic homeostasis that mimic endotoxemia and septic shock syndrome. Anti-cachectin antibodies protect against the lethal effects of septic shock and cachexia, suggesting that this mediator has a central role as a trigger to the inflammatory and deleterious host responses to infection. Future investigations will undoubtedly be directed towards the effects of inhibiting cachectin/TNF in the treatment of the complications of infectious disease.