IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in no and hepatic NF-kappa B

After a severe trauma, such as a cutaneous thermal injury, an increase in h epatocyte apoptosis has been associated with hepatocyte damage and Impairme nt in hepatic function. Insulinlike growth factor-I (IGF-I) exerts anti-apo ptotic effects in several organs, thus improving organ homeostasis. The pur pose of the present study was to determine whether IGF-l in combination wit h its principle binding protein-3 (BP-3) attenuates liver damage after a bu rn and whether this attenuation is through signals of the apoptotic-prolife rative axis of hepatocytes. Sprague-Dawley rats (56 males) received a 60% t otal body surface area third-degree scald burn and were randomly divided to receive either rhIGF-I/BP3 (10 mg/kg/day so.) or saline (control). Serum a spartate transaminase (AST) and nitric oxide (NO), and hepatocyte prolifera tion and apoptosis, were measured on postburn days 1, 2, 5, and 7. Hepatic interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA and hepatic nuclear-factor kappaB (NF-kappaB) were determined at 1 and 2 days postburn. IGF-I/BP-3 decreased serum AST and Increased serum NO at 1, 2, and 5 days after burn when compared with controls (P<0.05). IGF-I/BP- 3 increased hepatocyte proliferation on the first day after burn and decrea sed hepatocyte apoptosis at day 7 postburn when compared with controls (P<0 .05). IGF-I/BP-3 decreased hepatic IL-1 beta and TNF-alpha mRNA 1 day after burn (P<0.05). IGF-I/BP-3 further increased hepatic NF-<kappa>B concentrat ion I and 2 days postburn when compared with controls (P<0.05). Recombinant hIGF-I in combination with Its principle binding protein conserves hepatic homeostasis, which is associated with a transient Increase in hepatocyte p roliferation and decrease in hepatocyte apoptosis possibly through NO and h epatic NF-<kappa>B.