The effect of growth hormone on gut mucosal homeostasis and cellular mediators after severe trauma.
BACKGROUND
Gut mucosal integrity and function is impaired after severe trauma with associated increases in small bowel epithelial cell apoptosis and decreases in cell proliferation. Growth hormone improves gastrointestinal function during chemotherapy and has anabolic effects on protein synthesis. The purpose of this study was to determine whether growth hormone can improve small bowel homeostasis after injury and by which cellular mechanisms these changes occur.


METHODS
Rats were pair-fed, given a thermal trauma, and received saline (n = 28) or GH (2.5 mg/kg every 24 h, n = 28). Small intestine and serum were taken at 1, 2, 5, and 7 days after injury. Measures were mucosal apoptosis, proliferation, villous morphology, apoptotic, and proliferative mediators, such as Caspases-3, -8, Fas and Fas-Ligand, Bcl-2, and Bcl-x. In addition serum cytokines were determined.


RESULTS
Gut epithelial cell apoptosis and proliferation were increased in both groups after the thermal injury (P < 0.05). GH had neither an effect on small bowel epithelial cell apoptosis or proliferation, nor dependent cellular mediators after thermal injury. However, GH significantly improved villous morphology (height and cell number) when compared with controls (P < 0.05). RhGH was found to significantly increase serum TNF-alpha compared to controls (P < 0.05).


CONCLUSIONS
Growth hormone improves small bowel homeostasis after severe trauma independent from small bowel epithelial cell apoptosis or proliferation, probably by increasing the life span.
Jeschke
Marc G
MG
Shriners Hospital for Children and Department of Surgery, University Texas Medical Branch, Galveston, Texas 77550, USA. Mcjeschke@hotmail.com
Herndon
David N
DN
Finnerty
Celeste C
CC
Bolder
Ullrich
U
Thompson
James C
JC
Mueller
Ulla
U
Wolf
Steven E
SE
Przkora
Rene
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002056:Burns / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008871:Microvilli / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I