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

Jeschke, Marc G. MD; Herndon, David N. MD, FCCM; Wolf, Steven E. MD; DebRoy, Meelie A. MD; Rai, Jyoti MD; Thompson, James C. MD; Barrow, Robert E. PhD

Laboratory Investigations
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Objective: Hepatocyte growth factor (HGF) has been shown to modulate the acute-phase responsein vitro.The specificin vivorole 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 responsein vivoafter burn and causes changes in liver morphology.

From the Shriners Hospital for Children and the Department of Surgery, University Texas Medical Branch, Galveston, TX.

Supported, in part, by Grant 8010 from the Shriners Hospital for Children and by Snow Brand Milk Products.

Presented, in part, at the 1998 American Gastroenterological Association Meeting, New Orleans, LA, May 1998.

The HGF was kindly provided by Snow Brand Milk Products and the Research Institute of Life Science (Tochigi, Japan).

Copyright © by 2000 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.