Infiltrating neutrophils in bile duct-ligated livers do not promote hepatic fibrosis.

Bile duct obstruction causes rapid infiltration of neutrophils into the liver and leads ultimately to hepatic fibrosis. In this study, we assessed whether neutrophils play an active role in the pathogenesis of hepatic fibrosis under conditions of biliary obstruction. We performed bile duct ligation (BDL) on rats, some of which were depleted of neutrophils by means of an anti-neutrophil antiserum. Rats treated with the antiserum had 48% fewer neutrophils than control rats. Despite this, they showed no difference in either bile duct proliferation or hepatic fibrogenesis after BDL compared with control rats. In a second set of experiments, we performed BDL on mice with an underlying defect in neutrophil function due to transgenic expression of interleukin-8. Mice with neutrophil dysfunction deposited less (-22%) collagen in their livers after BDL than wild-type mice, but the difference was not statistically significant. In summary, data from two independent rodent models indicate that infiltrating neutrophils do not influence hepatic fibrogenesis following bile duct obstruction. The findings suggest that neutrophils play little if any role in the immunomodulation of liver fibrosis.