title: Tumor necrosis factor induces skeletal muscle protein breakdown in rats.
abstract: The metabolic response to infection includes loss of lean tissue and increased nitrogen excretion. The loss of muscle tissue during infection results in large part from accelerated skeletal muscle protein breakdown. Recent studies suggest that macrophage-derived products secreted during infection may signal increased muscle proteolysis. To test this, in the present report the ability of interleukin (IL-1) and tumor necrosis factor (TNF) to enhance muscle proteolysis was examined. Young rats were injected intravenously with either recombinant human IL-1 or TNF. For comparison some rats were injected with bacterial endotoxin. Eight hours after each treatment, the extensor digitorum longus muscles were isolated and incubated in vitro to assess muscle proteolysis by measuring tyrosine and 3-methyl-L-histidine release by the incubated muscles. Treatment of rats with either IL-1, TNF, or endotoxin all induced fever, increased serum lactate, and reduced serum zinc levels. Despite similar metabolic changes, muscle proteolysis responded differently. As expected, endotoxin treatment enhanced muscle protein breakdown, whereas IL-1 treatment was without effect. On the other hand, TNF was effective in accelerating muscle protein breakdown. TNF addition in vitro failed to enhance muscle proteolysis by incubated muscles, suggesting that its effects may be mediated in an indirect manner; however, a direct mode of action cannot yet be ruled out. Overall, the data indicate that the acute administration of TNF can signal increased muscle proteolysis similar to that observed during infection.
authors.affiliation: Department of Medicine, University of California, School of Medicine, Davis, Sacramento 95817.
authors.forename: M N
authors.initials: MN
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008762:Methylhistidines / Q000032:analysis; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D004731:Endotoxins; D007375:Interleukin-1; D008762:Methylhistidines; D009124:Muscle Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C028118:3-methylhistidine