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.


METHODS
Prospective, randomized, laboratory study.


METHODS
Shriners Hospital for Children and University of Texas Medical Branch laboratories.


METHODS
Fifty-six male Sprague-Dawley rats (weight range, 300-325 g).


METHODS
Animals received a 60% total body surface area third-degree scald burn and were randomly divided to receive either 400 microg/kg/day i.v. HGF or saline (control).


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 alpha2-macroglobulin concentrations on postburn days 2, 5, and 7 compared with controls (p<.05). Serum interleukin-6 and tumor necrosis factor-alpha 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-alpha 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.
Jeschke
M G
MG
Shriners Hospital for Children and the Department of Surgery, University Texas Medical Branch, Galveston, USA.
Herndon
D N
DN
Wolf
S E
SE
DebRoy
M A
MA
Rai
J
J
Thompson
J C
JC
Barrow
R E
RE
D000209:Acute-Phase Proteins / Q000187:drug effects / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001830:Body Surface Area; D002056:Burns / Q000150:complications* / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D017228:Hepatocyte Growth Factor / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000187:drug effects / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000187:drug effects / Q000378:metabolism
D000209:Acute-Phase Proteins; D016207:Cytokines; D012709:Serum Albumin; D014168:Transferrin; D000511:alpha-Macroglobulins; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I