Sepsis and cirrhosis in growing animals: description of a new experimental model and its pathological and immunological reliability

Abstract

OBJECTIVES: In cirrhotic children, infection events and sepsis are more frequent and more severe due to immune dysfunction. The objectives of the current study were therefore to develop an experimental model of infection and sepsis in cirrhotic weaning growing rats, by the use of bile duct ligation (BDL) and cecal ligation and puncture (CLP). Additionally, the correlation of the clinico-histopathological data and serial cytokine levels in septic cirrhotic and non-cirrhotic animals was studied. METHODS: Young Wistar rats of age 21 days and of weight between 70-90 g were divided into 12 groups according to the surgical procedure performed: sham (sacrificed after 2 or 4 weeks), BDL (sacrificed after 2 or 4 weeks), CLP (2- or 4-week old animals sacrificed after 12 or 24 hours), BDL+CLP (2- or 4-week old animals sacrificed after 12 hours). Histopathological studies and determination of serum levels of cytokines IL-1 beta, IL-10, and TNF-alpha, for studies of systemic infection, were performed. Murine sepsis scores (MSS) based on the clinical aspects just before euthanasia were also included. RESULTS: A transitory increase in IL-1, IL-10, and TNF-alpha levels was observed, with different patterns according to the groups. Two-hit groups tended to present with higher values of serum cytokines and histopathological scores than their septic non-cirrhotic counterparts. There was a correlation between mortality rate and MSS (p<0.0001). CONCLUSION: The model is feasible and may be utilized in studies on liver cirrhosis and infection in growing animals.

Keywords

• Cirrhosis
• Immune Dysfunction
• Endotoxemia
• Experimental Cirrhosis
• Biliary Obstruction
• Biliary Cirrhosis