Two-hit rat model of short bowel syndrome and sepsis: independent of total parenteral nutrition, short bowel syndrome is proinflammatory and injurious to the liver.
BACKGROUND
Infants with short bowel syndrome (SBS) are at a high risk for infectious complications and liver failure. We hypothesized that SBS, independent of total parenteral nutrition, is a proinflammatory state that is magnified by sepsis.


METHODS
Sprague-Dawley rats were divided into 2 groups: sham laparotomy (SH, n = 10) or 75% small bowel resection (n = 10). After 14 days, each group underwent a second sham laparotomy (SH/SH and SBS/SH) or cecal ligation and puncture, followed 16 hours later by cecal excision and peritoneal washout (SH/sepsis and SBS/sepsis). Animals were killed 56 hours later.


RESULTS
The SBS rats had higher serum levels of interleukin (IL) 6 vs SH (355 +/- 99 vs 104 +/- 71 pg/mL, P < .05). Liver injury scores were higher in SBS/sepsis compared with SBS/SH animals (3.7 +/- 0.7 vs 1.9 +/- 0.3, P < .05). Hepatic messenger RNA levels of IL-6 (12.8-fold change [FC]) and tumor necrosis factor alpha (5.65 FC) were elevated in SBS vs SH rats; and IL-6 (114 FC), tumor necrosis factor alpha (3.87 FC), and Toll-like receptor 4 (7.65 FC) were increased in SBS/sepsis compared with SH/sepsis animals.


CONCLUSIONS
Our results suggest that SBS, independent of total parenteral nutrition, is a proinflammatory state and that sepsis induces an exaggerated proinflammatory cytokine response that may play an important role in liver damage and may be mediated by Toll-like receptor 4.
Aprahamian
Charles J
CJ
Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, AL 35233, USA.
Chen
Min
M
Yang
Yingkui
Y
Lorenz
Robin G
RG
Harmon
Carroll M
CM
D000818:Animals; D002432:Cecum / Q000293:injuries / Q000382:microbiology; D005786:Gene Expression Regulation; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D008026:Ligation; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D023421:Models, Animal; D010289:Parenteral Nutrition, Total; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000503:physiopathology*; D012778:Short Bowel Syndrome / Q000150:complications / Q000503:physiopathology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D015850:Interleukin-6; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha