The effect of interleukin-1 alpha and the glucocorticoid receptor blocker RU 38486 on total and myofibrillar protein breakdown in skeletal muscle.

The purpose of the present study was to test the hypothesis that muscle proteolysis induced by interleukin-1 alpha (IL-1 alpha) is mediated by glucocorticoids. Male Sprague-Dawley rats, weighing 40-60 g, were treated with recombinant IL-1 alpha (rIL-1 alpha), 300 micrograms/kg in three divided intraperitoneal doses over 16 hr, or corresponding control injections. Groups of rats received the glucocorticoid receptor blocker RU 38486 by gavage (15 mg/kg in three divided doses over 16 hr) or were subjected to sham-gavage. In other experiments we tested the effectiveness of the same dose of RU 38486 to block muscle proteolysis in rats treated with corticosterone (200 mg/kg in two divided doses over 16 hr). Total and myofibrillar protein breakdown rates in incubated extensor digitorum longus muscles were determined by measuring release of tyrosine and 3-methylhistidine, respectively. Administration of rIL-1 alpha increased total and myofibrillar protein breakdown by 49 and 134%, respectively. This effect of the cytokine was not affected by RU 38486. The same dose of RU 38486, however, completely blocked the increase in total and myofibrillar protein breakdown induced by corticosterone. The results suggest that muscle proteolysis induced by the administration of rIL-1 alpha is not mediated by glucocorticoids.