Burn-induced changes in IGF-I and IGF-binding proteins are partially glucocorticoid dependent

The purpose of the present study was to determine whether burn-induced changes in various components of the insulin-like growth factor (IGF) system are mediated by the actions of endogenous glucocorticoids or tumor necrosis factor (TNF). To address this aim, a 30% total body surface area full-thickness scald burn was produced in anesthetized rats, and the animals were studied 24 h later. Separate groups of time-matched control and burned rats were pretreated with either an antagonist to glucocorticoids (RU-486) or to TNF (TNF-binding protein; TNFBP). Thermal injury decreased the plasma concentration of IGF-I (38%) as well as the IGF-I mRNA abundance in muscle and kidney (31 and 48%, respectively). While RU-486 prevented the burn-induced decrease in plasma IGF-I, it did not ameliorate the reduction in tissue IGF-I mRNA. Burn increased the plasma concentration of IGF-binding protein (IGFBP)-1 as well as the mRNA content of IGFBP-1 in liver and kidney (15- to 20-fold). These burn-induced increases were partially or largely prevented by RU-486. In contrast, burn decreased the plasma concentration of IGFBP-3 (30%). Burn concomitantly decreased hepatic IGFBP-3 mRNA abundance (42%) but increased IGFBP-3 mRNA in kidney and muscle (50% and 10-fold, respectively). RU-486 largely prevented the burn-induced changes in IGFBP-3 mRNA in kidney and muscle but failed to attenuate the decreases in plasma and liver. Finally, burn injury decreased hepatic acid-labile subunit (ALS) mRNA by 80% and increased the mRNA content of IGFBP-related protein-1 (mac25) in liver by twofold, and these changes were not modified by pretreatment with RU-486. The above-mentioned changes in the IGF system were associated with a burn-induced decrease in muscle protein content that was prevented by RU-486. TNFBP failed to completely ameliorate any of the burn-induced changes in the IGF system. These results demonstrate that glucocorticoids, but not TNF, mediate many but not all of the burn-induced changes in the IGF system.