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Updated: Aug 9, 2026
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct obstruction in experimental
Sujit Kumar Mohanty1, Pranavkumar Shivakumar, Gregg Sabla
1Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. sujit.mohanty@cchmc.org
Background:
Livers of infants with biliary atresia and of neonatal mice infected with rotavirus (RRV) have increased expression of interferon-gamma (IFNgamma) and interleukin (IL)-12. While the expression of IFNgamma regulates the obstruction of extrahepatic bile ducts by lymphocytes, the role of IL-12 in the pathogenesis of biliary obstruction is unknown. Based on the role of IL-12 as a key proinflammatory cytokine, we hypothesized that loss of IL-12 prevents the obstruction of extrahepatic bile ducts.
Methods:
IL12-knockout (IL-12KO) and wild type mice were injected with RRV or saline at day 1 of age and monitored for the development of symptoms. The cellular and molecular phenotypes were determined at days 3, 7, and 14 by real-time PCR and flow cytometry.
Results:
RRV infection of IL-12KO mice resulted in growth failure, jaundice/acholic stools, and decreased survival similar to wild-type mice. IL-12KO mice had a remarkable neutrophil-rich portal inflammation and epithelial sloughing of extrahepatic bile ducts. Loss of IL-12 decreased but did not abolish the hepatic expression of IFNgamma, displayed a remarkable increase in expression of TNFalpha, IFNalpha, IFNbeta and decreased expression of IL-4 and IL-5.
Conclusion:
Loss of IL-12 did not modify the progression of bile duct obstruction in experimental biliary atresia. However, the inflammatory response was predominantly neutrophil-based and displayed a Th1 response in the absence of IL-12.
