Interleukin-1 beta suppresses growth hormone-induced acid-labile subunit mRNA levels and secretion in primary hepatocytes.

Cytokines are thought to mediate the catabolic states induced by infection and trauma. Recent evidence suggests that the cytokine interleukin-1 beta (IL-1 beta) directly inhibits the anabolic insulin-like growth factor (IGF)-I: growth hormone (GH) axis. The biological activity of circulating IGF is regulated by the hepatocyte derived, GH-dependent acid-labile subunit (ALS) of the 140-kDa IGF binding protein (IGFBP) complex. ALS buffers the growth and metabolic effects of the insulin-like growth factors by sequestering them in a ternary complex with IGFBP-3. To determine whether IL-1 beta has a direct effect on hepatic ALS production, we have examined its effect on ALS mRNA levels and secretion in hepatocytes under GH-induced and basal conditions. In the presence of GH (30 ng/mL) half-maximal reduction of ALS mRNA levels and secretion was induced by between 0.3-3 ng/mL rhIL-1 beta (P < 0.05). However, under basal conditions IL-1 beta had no significant effect on ALS mRNA levels, and only a slight suppression of secretion. Our study suggests that IL-1 beta regulates ALS gene expression and secretion in a way that is dependent, in part, on interaction with the GH signalling pathway.