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

Arch Surg. 1992;127(2):170-174.

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- (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.

(Arch Surg. 1992;127:170-174)

Author Affiliations
From the Department of Surgery (Drs Zamir, Hasselgren, Frederick, Higashiguchi, and Fischer), University of Cincinnati (Ohio) Medical Center, and the Department of Pathology (Dr Kunkel), University of Michigan Medical School, Ann Arbor.

Footnotes
Accepted for publication November 2, 1991.

Presented at the 11th Annual Meeting of the Surgical Infection Society, Fort Lauderdale, Fla, April 9, 1991.

Reprint requests to Department of Surgery, University of Cincinnati, 231 Bethesda Ave, Cincinnati, OH 45267-0558 (Dr Hasselgren).

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