Evidence That Tumor Necrosis Factor Participates in the Regulation of Muscle Proteolysis During Sepsis

Oded Zamir, Per Olof Hasselgren, Steven L. Kunkel, Janice Frederick, Takashi Higashiguchi, Josef E. Fischer

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Abstract

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-α (300 μg/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 shamoperation. 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.

Original languageEnglish
Pages (from-to)170-174
Number of pages5
JournalArchives of Surgery
Volume127
Issue number2
DOIs
Publication statusPublished - 02-1992

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All Science Journal Classification (ASJC) codes

  • Surgery

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