Abstract
It has been proposed that many of the physiologic and metabolic changes that occur during critical illness and malignancy are mediated by the cytokine tumor necrosis factor alpha/cachectin (TNF). To test this hypothesis, a study of the metabolic responses that occurred during 5 days of continuous intravenous (I.V.) infusion of TNF both in rats and tumor-bearing humans was conducted. TNF administration was associated with anorexia, fluid retention, acute phase responses, and negative nitrogen balance. In both species, changes in nitrogen balance were related to the onset of anorexia and not to the development of hypermetabolism and accelerated net tissue breakdown. TNF may represent the primary afferent stimulus inducing many of the metabolic changes that occur during critical illness, but it is not solely responsible for the accelerated net proteolysis that occurs in these patients.