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 1 2005

Keywords

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

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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