Abstract: |
The liver plays an important role in the acute-phase response to sepsis and injury, and host survival often depends upon an adequate hepatic response. Many of the metabolic sequelae to sepsis and injury are mediated by interleukin-1. This study was undertaken to investigate the impact of interleukin-1 upon hepatic metabolism and whether this mediator acted directly upon the liver. Interleukin-1 (5 rabbit pyrogen dose units) was administered to male Fisher F344 rats (175 to 200 g), and hepatocytes were isolated at three time periods; 2 to 4, 6 to 10, and 12 to 14 hours following an intraperitoneal injection. Alanine transport, gluconeogenesis, nonsecretory protein synthesis, and oxygen consumption were measured simultaneously in freshly isolated hepatocytes. Interleukin-1 stimulated initial rates of alanine uptake over a four-minute period. Peak stimulation of gluconeogenesis occurred at six to ten hours (0.52 ± .14 v 0.08 ± .01 nmol alanine converted/106 cells/min, P < 0.05); nonsecretory protein synthesis was significantly stimulated at 12 to 14 hours (2.1 ± .7 v 0.7 ± 0.1 nmol valine converted/106 cells/min, P < 0.05). These enhanced metabolic processes were associated with an increased oxygen consumption, with peak oxygen utilization occurring at six to ten hours (69 ± 2 v 25 ± 7 nmol of oxygen consumed 106 cells/min, P < 0.05). In order to examine if interleukin-1 exerted its effect directly upon the liver, hepatocytes from normal rats were incubated in vitro with this mediator for two hours. Under these experimental conditions, interleukin-1 did not reproduce the stimulatory effect obtained following in vivo administration. These data show that interleukin-1 stimulates many aspects of hepatic metabolism in a time-dependent fashion but may not act directly upon hepatocytes in a cell suspension. © 1986. |