Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis

O. Zamir, P. O. Hasselgren, S. L. Kunkel, J. Frederick, T. Higashiguchi and J. E. Fischer
Department of Surgery, University of Cincinnati, OH 45267-0558.

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.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Tumor necrosis factor inhibits growth hormone-mediated gene expression in hepatocytes
Ahmed et al.
Am. J. Physiol. Gastrointest. Liver Physiol. 2006;291:G35-G44.
ABSTRACT | FULL TEXT  

Interleukin-1 inhibits the induction of insulin-like growth factor-I by growth hormone in CWSV-1 hepatocytes
Shumate et al.
Am. J. Physiol. Gastrointest. Liver Physiol. 2005;289:G227-G239.
ABSTRACT | FULL TEXT  

Body weight, body composition, and bone turnover changes in patients with spondyloarthropathy receiving anti-tumour necrosis factor {alpha} treatment
Briot et al.
Ann Rheum Dis 2005;64:1137-1140.
ABSTRACT | FULL TEXT  

Tumor necrosis factor mediates hepatic growth hormone resistance during sepsis
Yumet et al.
Am. J. Physiol. Endocrinol. Metab. 2002;283:E472-E481.
ABSTRACT | FULL TEXT  

Glutamine Alimentation in Catabolic State
Boelens et al.
J. Nutr. 2001;131:2569S-2577.
ABSTRACT | FULL TEXT  

The Role of Tumor Necrosis Factor-alpha (TNF-{alpha}) in Skeletal Muscle Regeneration: Studies in TNF-{alpha}(-/-) and TNF-{alpha}(-/-)/LT-{alpha}(-/-) Mice
Collins and Grounds
J. Histochem. Cytochem. 2001;49:989-1002.
ABSTRACT | FULL TEXT  

Hyperthermia stimulates energy-proteasome-dependent protein degradation in cultured myotubes
Luo et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000;278:R749-R756.
ABSTRACT | FULL TEXT  

TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis
Cooney et al.
Am. J. Physiol. Endocrinol. Metab. 1999;276:E611-E619.
ABSTRACT | FULL TEXT  

A Sustained Rat Model for Studying the Long-Lasting Catabolic State of Sepsis
Breuille et al.
Infect. Immun. 1999;67:1079-1085.
ABSTRACT | FULL TEXT  

Sepsis in mice stimulates muscle proteolysis in the absence of IL-6
Williams et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 1998;275:R1983-R1991.
ABSTRACT | FULL TEXT  

Cytokine modulation by PX differently affects specific acute phase proteins during sepsis in rats
Voisin et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 1998;275:R1412-R1419.
ABSTRACT | FULL TEXT  

Differential regulation of skeletal muscle protein turnover by insulin and IGF-I after bacteremia
Vary et al.
Am. J. Physiol. Endocrinol. Metab. 1998;275:E584-E593.
ABSTRACT | FULL TEXT  

Mechanisms of Muscle Wasting -- The Role of the Ubiquitin-Proteasome Pathway
Mitch and Goldberg
NEJM 1996;335:1897-1905.
FULL TEXT  

Invited Review: Cytokine Mediators of Malnutrition: Clinical Implications
Hardin
Nutr Clin Pract 1993;8:55-59.
ABSTRACT  

TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation
Lang et al.
Am. J. Physiol. Endocrinol. Metab. 2002;282:E336-E347.
ABSTRACT | FULL TEXT