Excessive Inflammation but Decreased Immunological Response Renders Liver Susceptible to Infection in Bile Duct Ligated Mice

Abstract

Obstructive jaundice (OJ) is associated with increased surgical morbidity and infectious complication. The aim of the current study was to clarify the mechanism of excessive inflammation and susceptibility to infection in OJ. C57/BL6 mice were subjected to bile duct ligation (BDL) or sham surgery. Expression tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, inducible protein-10, and interleukin (IL)-10, activation of nuclear factor kappa B, fluorescence activated cell sorter analysis, serum alanine aminotransferase levels, and histology were examined. Survival after lipopolysaccharide (LPS) administration or cecal ligation and puncture 3 or 14 d after surgery was determined. IL-1beta and interferon-gamma expression was examined after LPS administration. OJ induced nuclear factor kappa B activation and increased expression of macrophage inflammatory protein-2, which caused significant increases in neutrophil recruitment. Serum alanine aminotransferase levels increased consistent with histological observations in OJ. Mononuclear cells were recruited in the liver after BDL associated with monocyte chemoattractant protein-1 up-regulation. The recruitment of NK and T cells was varied, consistent with IP-10 expression during the time course of OJ. IL-10 expression was significantly up-regulated 14 d after BDL. After LPS administration, the mice at 3 d after BDL and at 3 and 14 d after sham surgery were all still alive, but all mice at 14 d after BDL died. After LPS administration, IL-1beta significantly increased in the mice at 14 d after BDL. Immune response such as expression of pro- and anti-inflammatory mediators and recruitment of immune cells may thus differ over the time course of OJ. Prolonged OJ may cause excessive inflammation, thus result in susceptibility to infection.