EFFECTS OF TUMOR-NECROSIS-FACTOR ON PROTEIN-METABOLISM

Increased skeletal muscle breakdown and negative nitrogen balance are features of sepsis that may be mediated by cytokines. The effects of t umour necrosis factor (TNF) on protein metabolism were studied. When a dministered to anaesthetized dogs (0.57 x 10(5) units per kg body-weig ht over 6 h), TNF caused urinary nitrogen excretion to increase (mean( s.e.m.) 165(15) mg kg-1 for dogs that received TNF versus 113(8) mg kg -1 for control animals, P < 0.01). Amino acid nitrogen release from th e hindlimbs showed no change over the study period, indicating that th e additional urinary nitrogen was not derived from peripheral protein stores. In a second study the same dose of TNF or saline was infused a fter the intestine had been removed. The mean(s.e.m.) urinary nitrogen excretion in control dogs that had undergone enterectomy (101(7) mg k g-1) was similar to that of intact animals, and addition of TNF did no t significantly increase nitrogen excretion (86(18) mg kg-1). The resu lts suggest that nitrogen excreted in the urine during administration of TNF is derived, at least initially, from the intestinal tract.