THE COMBINATION OF GROWTH HORMONE WITH HEPATOCYTE GROWTH FACTOR ALTERS THE ACUTE PHASE RESPONSE

Recombinant human growth hormone (rhGH) and hepatocyte growth factor (HGF) have both been shown to individually modulate hepatic acute phase reactant proteins and cytokine expression following trauma through different pathways. Recombinant hGH has also been shown to decrease serum and hepatic HGF concentrations after a thermal injury. We hypothesized that the combination of rhGH plus HGF improves the burn-induced acute phase response. Fifty-six male Sprague-Dawley rats received a 60% TBSA third-degree scald burn and were randomly divided to receive either rhGH (2.5 mg/kg/day sc.) plus HGF (200 microg/kg i.v. every 12 h) or placebo (saline). Rats were sacrificed on post-burn days 1, 2, 5, or 7 and serum constitutive and acute phase proteins, TNF-alpha, IL-1beta, IL-6 and liver total protein measured. Hepatic cytokine gene expression, triglyceride concentration, and hepatocyte proliferation were also measured. In rats receiving rhGH/HGF, serum albumin increased on days 5 and 7 and transferrin on day 7 after burn compared to placebo (P<0.05). Haptoglobin decreased 5 days after burn compared to placebo (P<0.05). RhGH/HGF increased serum TNF-alpha on day 2 after burn, while it decreased serum IL-1beta on day 1 after burn compared with placebo (P<0.05). RhGH/HGF had no effect on hepatic cytokine gene expression compared with placebo. Liver total protein content and hepatocyte proliferation increased on days 1, 2, 5, and 7 after burn with rhGH/HGF treatment (P<0.05). These findings indicate that rhGH in combination with HGF exert additive effects on constitutive hepatic proteins and partial inhibitory effects on acute phase protein and cytokine expression. RhGH/HGF has a strong mitogenic effect on hepatocytes.