Interleukin-6 and dexamethasone work coordinately to augment hepatic amino acid transport

The in vivo effects of interleukin-6 (IL-6) and dexamethasone (Dex) on amino acid transport in rat liver were studied employing hepatic plasma membrane vesicles (HPMVs). Adult rats were treated with Dex (0.5 mg/kg) and subsequently with varying concentrations if IL-6 (10, 50, or 150 micrograms/kg). The HPMVs were prepared by Percoll density gradient centrifugation. The activities of System A, System N, and System y+ transport proteins were evaluated by tritiated uptake of their respective amino acids (methyl-aminoisobutyric acid [MeAIB], glutamine, and arginine). System A activity was increased in response to low doses of IL-6. Dex alone increased System A and had an additive effect to enhance transport in response to IL-6. System N was stimulated by higher doses of IL-6 in a dose-dependent manner. Dexamethasone had no effect by itself on System N activity but worked synergistically to enhance the effect of IL-6 even at low doses. System y+ activity was increased by Dex but IL-6 did not alter arginine transport. Kinetic analysis of the increases in System A and N showed the increases to be related to an increase in the Vmax (maximal transport velocity) for the carrier with no significant change in Km, carrier affinity. We conclude that IL-6 and glucocorticoids work in a coordinated fashion to enhance hepatic amino acid uptake.