The role of tumor necrosis factor (TNF) in the regulation of muscle protein turnover was studied in rats. Protein synthesis and total and myofibrillar protein breakdown rates were measured in incubated extensor digitorum longus muscles. Intraperitoneal administration of recombinant TNF-alpha (300 micrograms/kg of body weight) increased total and myofibrillar protein breakdown rates by 28% and threefold, respectively, with no effect on protein synthesis. In subsequent experiments, sepsis was induced by cecal ligation and puncture or a sham-operation was performed. Rats received TNF antiserum (1 mL/100 g of body weight) or control serum 2 hours before cecal ligation and puncture or sham-operation. Treatment with TNF antiserum reduced the mortality rate from 25% to 5% following cecal ligation and puncture. The treatment had no effect on protein synthesis but reduced total and myofibrillar protein breakdown rates by 26% and 39%, respectively, in septic animals. Results suggest TNF is involved in the regulation of sepsis-induced muscle proteolysis.

No abstract

The influence of sepsis on intestinal protein synthesis was studied in rats. Sepsis was induced by caecal ligation and puncture (CLP); control rats were sham-operated. Protein synthesis was measured in vivo in the jejunum and ileum following a flooding dose of [14C]leucine. At 8 h after CLP the protein synthesis rate was increased by approx. 15% in jejunal mucosa, and at 16 h after CLP, the protein synthesis rate was increased by 50-60% in the mucosa and seromuscular layer of both jejunum and ileum. In a second series of experiments, rats were treated with recombinant tumour necrosis factor alpha (rTNF alpha) or recombinant interleukin-1 alpha (rIL-1 alpha) administered at a total dose of 300 micrograms/kg body weight over 16 h. Control rats received corresponding volumes of solvent. Treatment with rTNF alpha resulted in an approx. 25% increase in mucosal protein synthesis in jejunum. Following treatment with rIL-1 alpha, protein synthesis increased by 25% in jejunal mucosa and almost doubled in ileal mucosa. The results suggest that sepsis stimulates intestinal protein synthesis and that this response may, at least in part, be mediated by TNF and/or IL-1.