Tumour necrosis factor (TNF) and interleukin-1 (IL-1) induce muscle proteolysis through different mechanisms

The purpose of this study was to test the hypothesis that muscle proteolysis induced by TNF or IL-1 is mediated by glucocorticoids. Rats were treated with 300 mug kg(-1) of recombinant human preparations of IL-1alpha (rIL-1alpha) or TNFalpha (rTNFalpha) divided into three equal intraperitoneal doses given over 16 h. Two hours before each cytokine injection, rats were given 5 mg kg(-1) of the glucocorticoid receptor blocker mifepristone RU 38486, by gavage or were gavaged with the vehicle. Eighteen hours after the first cytokine injection, total and myofibrillar protein breakdown rates were determined in incubated extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine, respectively. Total and myofibrillar proteolytic rates were increased following injection of rIL-1alpha or rTNFalpha. Proteolysis induced by rIL-1alpha was not altered by treatment with RU 38486. In contrast, the glucocorticoid receptor blocker inhibited the proteolytic effect of rTNFalpha. The results suggest that the proteolytic effect of TNF is mediated by glucocorticoids and that IL-1 induces muscle proteolysis through a glucocorticoid independent pathway.