IL-8 expression by biliary epithelial cells is associated with neutrophilic infiltration and reactive bile ductules

Background/Aims: Reactive bile ductule is a non-specific feature of various hepatobiliary diseases, and is not infrequently accompanied by neutrophilic infiltration. Recently, biliary epithelial cells have been shown to secrete cytokines and chemokines and to express components of the mucosal immune system such as Toll-like receptors. Methods and Results: We examined the expression of a neutrophil chemo-attractant, interluekin (IL)-8, in bile ductular cells to clarify the histogenesis of reactive bile ductules with neutrophilic infiltration using human liver tissues (eight cases of chronic viral hepatitis, seven cases of liver cirrhosis (LC), seven cases of sepsis, 11 cases of extrahepatic biliary obstruction (EBO), three cases of fulminant hepatitis (FH), five cases of primary biliary cirrhosis, and three cases of primary sclerosing cholangitis). Human neutrophil peptides 1-3 (HNP1-3) were used as markers of neutrophils. Immunohistochemically, IL-8 was detected in bile ductules in various diseased livers. HNP1-3-positive neutrophils were significantly dense around IL-8-positive bile ductules compared with IL-8-negative ductules in septic liver, LC, EBO, and FH. Experiments in vitro showed that cultured human biliary epithelial cells expressed and secreted IL-8 in response to lipopolysaccharide and also IL-1 beta and tumour necrosis factor-alpha. Conclusions: Neutrophilic infiltration around reactive bile ductules may be related to the IL-8 expressed in bile ductular epithelia, possibly induced by bacterial components and proinflammatory cytokines released locally.