In vivo administration of interleukin-1α induces muscle proteolysis in normal and adrenalectomized rats

The effect on muscle protein turnover of recombinant interleukin-1α (rlL-1α), 300 μg/kg body weight (BW) administered intraperitoneally (IP) in three divided doses over 18 hours, was studied in rats. Protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein, and total and myofibrillar protein breakdown rates were determined by measuring release of tyrosine and 3-methylhistidine, respectively, in incubated extensor digitorum longus muscles. To assess the role of glucocorticoids in rlL-1α-related metabolic alterations, plasma levels of corticosterone following rlL-1α injection and the effect of rlL-1α on muscle protein breakdown in adrenalectomized and sham-adrenalectomized rats were determined. Total and myofibrillar protein breakdown rates were increased by 45% and 167%, respectively, following treatment of normal rats with rlL-1α; muscle protein synthesis was not altered by the cytokine. Plasma corticosterone levels were markedly elevated following rlL-1α injection, with a maximal level occurring at 30 minutes. However, administration of rlL-1α resulted in increased total and myofibrillar protein breakdown rates in both adrenalectomized and shamadrenalectomized rats. The results suggest that increased muscle proteolysis following administration of rlL-1α is independent of glucocorticoids.