Hepatocyte growth factor modulates the hepatic acute-phase response in thermally injured rats

Objective: Hepatocyte growth factor (HGF) has been shown to modulate the acute-phase response in vitro. The specific in vivo role of HGF in this multifactorial response, however, remains unknown. This study examines the effects of exogenous HGF on the acute-phase response in thermally injured rats. Design: Prospective, randomized, laboratory study. Settings: Shriners Hospital for Children and University of Texas Medical Branch laboratories. Subjects: Fifty-six male Sprague-Dawley rats (weight range, 300-325 g). Intervention: Animals received a 60% total body surface area third-degree scald burn and were randomly divided to receive either 400 μg/kg/day iv HGF or saline (control). Measurements and Main Results: Serum acute-phase proteins, cytokines, and insulin-like growth factor (IGF)-I concentrations, as well as liver weight, protein and triglyceride content, IGF-I concentrations, and cytokine gene expression were measured 1, 2, 5, or 7 days after burn. Serum albumin was increased on days 2, 5, and 7 after burn, and transferrin was increased on day 7 after burn in HGF-treated rats compared with controls (p < .05). HGF increased α₂-macroglobulin concentrations on postburn days 2, 5, and 7 compared with controls (p < .05). Serum interleukin-6 and tumor necrosis factor-α were significantly higher within 2 days of burn in rats treated with HGF (p < .05). HGF increased the hepatic gene expression of tumor necrosis factor-α compared with controls (p < .05). Serum IGF-I decreased in rats receiving HGF 1, 2, and 5 days after burn, whereas liver IGF-I concentrations were higher on days 1 and 7 after burn compared with controls (p < .05). Hepatic protein concentrations were higher in the HGF group compared with controls on postburn days 1, 2, and 7, with a concomitant increase in total liver weight (p < .05). HGF exerted a strong mitogenic effect on hepatocytes 1 and 2 days after thermal injury compared with controls (p < .05). Conclusions: These findings suggest that HGF modulates the acute-phase response in vivo after burn and causes changes in liver morphology.