Interleukin-15 decreases proteolysis in skeletal muscle: a direct effect.

Incubation of rat isolated skeletal muscles (extensor digitorum longus) in the presence of 100 ng/ml of human recombinant interleukin-15 (IL-15) resulted in a significant decrease in total proteolytic rate, while it had no effect on total protein synthesis as measured by the incorporation of (14)C-phenylalanine into muscle protein. In addition, IL-15 had no effect on either amino acid uptake (as determined by the tissue uptake of labelled [1-(14)C]MeAIB) or alanine utilization by incubated skeletal muscles. Similarly, a single injection of IL-15 (100 microg/kg) in vivo did not result in any changes in amino acid uptake (as measured by the tissue uptake of alpha-[1-(14)C]AIB) or alanine metabolism, with the exception of alanine carbon incorporation into lipids, which was significantly increased in adipose tissue as a result of IL-15 administration. The results suggest that the main mechanism involved in the anabolic effects of IL-15 in skeletal muscle relies on a decrease in the proteolytic rate.