Cachetin/TNF: a macrophage protein that induces cachexia and shock.

Infection may elicit a clinical picture of metabolic and hemodynamic compromise that can deteriorate acutely to shock and death. Alternatively, injury or infection can lead a more indolent course, resulting in a progressive catabolic state that in time may advance to cachexia, organ failure, and death. Recent data suggest a complex array of endogenous humoral- and immunomodulators may orchestrate many of these detrimental responses. It has become clear that cachectin/tumor necrosis factor, a protein secreted by monocytes in response to many inflammatory, and injurious stimuli, holds a pivotal role in these host responses to injury. Circulating levels of this monokine is found in greater abundance and in higher frequency in seriously ill patients. The cellular metabolic response to cachectin/TNF simulates many of the pathophysiologic changes seen in injury and infection. Administration of cachectin/TNF to animals and man can mimic the clinical syndromes of cachexia or endotoxic shock, and neutralization of...

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