Nutritional, hepatic, and metabolic effects of cachectin/tumor necrosis factor in rats receiving total parenteral nutrition.

Abstract

In orally fed animals, infusion of cachectin/tumor necrosis factor (TNF) caused weight loss and muscular wasting, accompanied by anorexia. Despite muscle wasting, there were gains in weight and protein and DNA contents of the viscera, but no significant metabolic abnormalities. To observe the effect of cachectin/TNF on the nutritional-metabolic status, and without the confounding effect of anorexia, cachectin/TNF was infused into rats receiving total parenteral nutrition in sufficient amounts to induce weight gain in controls at the same rate as in orally fed rats. TPN prevented loss of body weight, but cachectin-treated animals had reduced nitrogen retention and carcass weight. By contrast, there were gains in visceral protein levels, which in the liver was due to a marked proliferation of biliary epithelium. In addition, cachectin-treated animals receiving TPN developed hyperglycemia, hyperosmolality, diuresis, and dehydration. They also had azotemia and cholestasis. In the absence of the effects of anorexia, cachectin reduced nitrogen retention and caused metabolic and multisystem dysfunction, comparable with the effects of clinical sepsis.