Indirect inhibition of myocyte RNA and protein synthesis by interleukin-1

Soluble mediators of the inflammatory response may directly influence myocardial function and metabolism in the absence of myocardial cell necrosis. Previous reported experimental data have demonstrated that the monokine interleukin-1 (IL-1) can produce myocardial depression and may influence muscle protein metabolism. To further investigate this hypothesis, IL-1 was added to neonatal rat cardiac muscle cell (MC) cultures with and without additional rat cardiac non-muscle cells (NMC). Incorporation of 3H-uridine or 14C-phenylalanine into acid-insoluble material was utilized as a measure of RNA or protein synthesis. IL-1 in concentrations of up to 500 units/ml had no effect on MC RNA or protein synthesis. When NMC were added to the MC culture, IL-1 exhibited a concentration-dependent inhibition of both RNA and protein synthesis, with effects apparent at concentrations as low as 5 units/ml. Supernatants from IL-1-treated NMC cultures exerted a dose dependent reduction on the incorporation of radiolabeled precursor into MC cultures, suggesting production of a soluble substance mediating the IL-1 effect. Supernatants from IL-1 treated rat skin fibroblasts or rat skeletal muscle myoblasts increased MC radiolabeled precursor incorporation slightly, in contrast to the decrease seen with NMC supernatant. Furthermore, IL-1 treated NMC supernatant had no inhibitory effect on skeletal myoblasts. We conclude that IL-1 decreases protein and RNA synthesis in MC cultures through a second mediator elaborated from the NMC population.