Stimulatory effect of interleukin-1 upon hepatic metabolism.
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/10(6) cells/min, P less than 0.05); nonsecretory protein synthesis was significantly stimulated at 12 to 14 hours (2.1 +/- .7 v 0.7 +/- 0.1 nmol valine converted/10(6) cells/min, P less than 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 10(6) cells/min, P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D014176:Protein Biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D015032:Zinc / Q000378:metabolism
D007375:Interleukin-1; D015032:Zinc; D000409:Alanine