The severity of cholestatic injury is modulated by the genetic background

Samuel M. Alaish, Manuel Torres, Marcella Ferlito, Chen Chih Sun, Antonio De Maio

Research output: Contribution to journalArticle

Abstract

Common bile duct ligation (CBDL) compromises the hepatic reticuloendothelial system by impairing the clearing of endotoxin and triggering an overwhelming inflammatory response. The response to endotoxin at the level of cytokine release and subsequent mortality depends on the genetic background in experimental mouse models. We hypothesized that the genetic make-up modulates the inflammatory responses after CBDL. The CBD was ligated in male A/J and B6 mice (8 weeks old). At 7 days post-CBDL, the presence of ascites was observed in 80% of B6 mice but in none of the A/J mice (P <0.001). B6 mice showed higher mortality than A/J mice (P <0.05). Both strains had marked cholestatic injury documented histologically. Liver chemistries were markedly elevated in both strains after injury. Plasma levels of the anti-inflammatory cytokine IL-10 were significantly higher in A/J than B6 mice at the 4- and 12-h time points (P <0.05), whereas proinflammatory cytokine TNF-α levels were significantly higher in B6 than A/J mice at 2 h (P <0.05). Both strains displayed activation of NF-κB after CBDL. In conclusion, the contrasting response observed after CBDL between A/J and B6 mice is largely attributable to genetic differences. Survival after CBDL was correlated with an increase in anti-inflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)412-416
Number of pages5
JournalShock
Volume24
Issue number5
DOIs
StatePublished - Nov 2005

Fingerprint

Common Bile Duct
Ligation
Wounds and Injuries
Cytokines
Endotoxins
Anti-Inflammatory Agents
Genetic Background
Mononuclear Phagocyte System
Mortality
Liver
Ascites
Interleukin-10
Theoretical Models

Keywords

  • Ascites
  • Common bile duct ligation
  • Cytokine
  • Mortality
  • Mouse

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

The severity of cholestatic injury is modulated by the genetic background. / Alaish, Samuel M.; Torres, Manuel; Ferlito, Marcella; Sun, Chen Chih; De Maio, Antonio.

In: Shock, Vol. 24, No. 5, 11.2005, p. 412-416.

Research output: Contribution to journalArticle

Alaish, Samuel M. ; Torres, Manuel ; Ferlito, Marcella ; Sun, Chen Chih ; De Maio, Antonio. / The severity of cholestatic injury is modulated by the genetic background. In: Shock. 2005 ; Vol. 24, No. 5. pp. 412-416.
@article{7024e1006d0b4cd0aa2a0bf1158bb600,
title = "The severity of cholestatic injury is modulated by the genetic background",
abstract = "Common bile duct ligation (CBDL) compromises the hepatic reticuloendothelial system by impairing the clearing of endotoxin and triggering an overwhelming inflammatory response. The response to endotoxin at the level of cytokine release and subsequent mortality depends on the genetic background in experimental mouse models. We hypothesized that the genetic make-up modulates the inflammatory responses after CBDL. The CBD was ligated in male A/J and B6 mice (8 weeks old). At 7 days post-CBDL, the presence of ascites was observed in 80{\%} of B6 mice but in none of the A/J mice (P <0.001). B6 mice showed higher mortality than A/J mice (P <0.05). Both strains had marked cholestatic injury documented histologically. Liver chemistries were markedly elevated in both strains after injury. Plasma levels of the anti-inflammatory cytokine IL-10 were significantly higher in A/J than B6 mice at the 4- and 12-h time points (P <0.05), whereas proinflammatory cytokine TNF-α levels were significantly higher in B6 than A/J mice at 2 h (P <0.05). Both strains displayed activation of NF-κB after CBDL. In conclusion, the contrasting response observed after CBDL between A/J and B6 mice is largely attributable to genetic differences. Survival after CBDL was correlated with an increase in anti-inflammatory cytokines.",
keywords = "Ascites, Common bile duct ligation, Cytokine, Mortality, Mouse",
author = "Alaish, {Samuel M.} and Manuel Torres and Marcella Ferlito and Sun, {Chen Chih} and {De Maio}, Antonio",
year = "2005",
month = "11",
doi = "10.1097/01.shk.0000183392.83272.97",
language = "English (US)",
volume = "24",
pages = "412--416",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - The severity of cholestatic injury is modulated by the genetic background

AU - Alaish, Samuel M.

AU - Torres, Manuel

AU - Ferlito, Marcella

AU - Sun, Chen Chih

AU - De Maio, Antonio

PY - 2005/11

Y1 - 2005/11

N2 - Common bile duct ligation (CBDL) compromises the hepatic reticuloendothelial system by impairing the clearing of endotoxin and triggering an overwhelming inflammatory response. The response to endotoxin at the level of cytokine release and subsequent mortality depends on the genetic background in experimental mouse models. We hypothesized that the genetic make-up modulates the inflammatory responses after CBDL. The CBD was ligated in male A/J and B6 mice (8 weeks old). At 7 days post-CBDL, the presence of ascites was observed in 80% of B6 mice but in none of the A/J mice (P <0.001). B6 mice showed higher mortality than A/J mice (P <0.05). Both strains had marked cholestatic injury documented histologically. Liver chemistries were markedly elevated in both strains after injury. Plasma levels of the anti-inflammatory cytokine IL-10 were significantly higher in A/J than B6 mice at the 4- and 12-h time points (P <0.05), whereas proinflammatory cytokine TNF-α levels were significantly higher in B6 than A/J mice at 2 h (P <0.05). Both strains displayed activation of NF-κB after CBDL. In conclusion, the contrasting response observed after CBDL between A/J and B6 mice is largely attributable to genetic differences. Survival after CBDL was correlated with an increase in anti-inflammatory cytokines.

AB - Common bile duct ligation (CBDL) compromises the hepatic reticuloendothelial system by impairing the clearing of endotoxin and triggering an overwhelming inflammatory response. The response to endotoxin at the level of cytokine release and subsequent mortality depends on the genetic background in experimental mouse models. We hypothesized that the genetic make-up modulates the inflammatory responses after CBDL. The CBD was ligated in male A/J and B6 mice (8 weeks old). At 7 days post-CBDL, the presence of ascites was observed in 80% of B6 mice but in none of the A/J mice (P <0.001). B6 mice showed higher mortality than A/J mice (P <0.05). Both strains had marked cholestatic injury documented histologically. Liver chemistries were markedly elevated in both strains after injury. Plasma levels of the anti-inflammatory cytokine IL-10 were significantly higher in A/J than B6 mice at the 4- and 12-h time points (P <0.05), whereas proinflammatory cytokine TNF-α levels were significantly higher in B6 than A/J mice at 2 h (P <0.05). Both strains displayed activation of NF-κB after CBDL. In conclusion, the contrasting response observed after CBDL between A/J and B6 mice is largely attributable to genetic differences. Survival after CBDL was correlated with an increase in anti-inflammatory cytokines.

KW - Ascites

KW - Common bile duct ligation

KW - Cytokine

KW - Mortality

KW - Mouse

UR - http://www.scopus.com/inward/record.url?scp=27644493649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644493649&partnerID=8YFLogxK

U2 - 10.1097/01.shk.0000183392.83272.97

DO - 10.1097/01.shk.0000183392.83272.97

M3 - Article

C2 - 16247325

AN - SCOPUS:27644493649

VL - 24

SP - 412

EP - 416

JO - Shock

JF - Shock

SN - 1073-2322

IS - 5

ER -