MECHANISMS OF HOST WASTING INDUCED BY ADMINISTRATION OF CYTOKINES IN RATS

This study determined the effects of chronic administration of the two principal proximate cytokines, interleukin-1 (IL-1) and tumor necrosi s factor (TNF), on host wasting in rats. The effects were compared wit h those observed in a matched pair-fed group to distinguish the contri bution from anorexia. Both TNF and IL-1 produced weight loss, net nitr ogen loss, and skeletal muscle catabolism and increased liver weight. Such effects were independent from and additive to those resulting fro m semistarvation. However, under equivalent nutritional conditions, TN F infusion led to a greater effect on muscle protein catabolism and li ver weight and caused liver protein anabolism, whereas only the group receiving IL-1 had altered glucose metabolism in the postabsorptive st ate. Tachyphylaxis was seen in the response of food intake over time a fter administration of IL-1. These actions define the two principal me chanisms for the development of protein calorie malnutrition that occu r because of cytokine action, anorexia producing semistarvation and an increased net protein catabolic rate reducing anabolic efficiency.