DECREASED ACID-LABILE SUBUNIT (ALS) LEVELS BY ENDOTOXIN IN-VIVO AND BY INTERLEUKIN-1-BETA IN-VITRO

The production by the liver of the three subunits of the growth hormon e (GH)-dependent 150 kDa complex (IGF-I, IGF-binding protein-3 and aci d-labile subunit or ALS) is primarily under the control of GH. Recent data have shown that, besides GH, endotoxin (LPS) and cytokines may re gulate the liver IGF-I gene. To investigate the potential regulation o f ALS by LPS, we measured serum ALS by immunoblot, 5 and 10 h after IP injection of LPS (250 or 750 mu g/100 g BW vs saline), in 4-week-old female Wistar rats (four per group). Ten hours after injection, serum ALS levels were reduced by 57% (Delta%) with the lower dose (P<0.05) a nd by 81% with the higher dose (P<0.01) by comparison with saline-trea ted rats. The decrease in ALS levels in response to LPS was not preven ted by exogenous GH. To investigate the role of interleukin (IL)-1 bet a in the regulation of ALS, primary cultured rat hepatocytes were expo sed to increasing concentrations of IL-1 beta. Cell exposure to IL-1 b eta markedly decreased both basal and GH-stimulated ALS levels (-70%, P<0.01) in a dose-dependent fashion, with the half-maximal inhibitory effect at concentrations of 0.1 ng/ml. Our results show that endotoxin induces a rapid decline in circulating ALS that is potentially mediat ed through IL-1 beta. By limiting the formation of the 150 kDa complex , this reduction in circulating ALS might contribute to the rapid decl ine in serum IGF-I observed in sepsis. (C) 1998 Churchill Livingstone.