High-dose IgG therapy mitigates bile duct-targeted inflammation and obstruction in a mouse model of biliary atresia

作者：Fenner Erika K^*; Boguniewicz Juri; Tucker Rebecca M; Sokol Ronald J; Mack Cara L

来源：Pediatric Research, 2014, 76(1): 72-80.

DOI：10.1038/pr.2014.46

BACKGROUND: A proposed etiology of biliary atresia (BA) entails virus-induced, progressive immune-mediated injury of the biliary system. Intravenous Ig (IVIg) has demonstrated clinical benefit in several inflammatory diseases. The aim of this study was to determine the therapeutic effects of high-dose IgG treatment in the rhesus rotavirus (RRV)-induced mouse model of BA.
METHODS: Newborn mice were infected with RRV, and jaundiced mice were given high-dose IgG or albumin control. Survival, histology, direct bilirubin, liver immune cell subsets, and cytokine production were analyzed.
RESULTS:There was no difference in overall survival between RRV-infected groups, however high-dose IgG resulted in decreased bilirubin, bile duct inflammation, and increased extrahepatic bile duct patency. High-dose IgG decreased vascular cell adhesion molecule-1, resulting in limited migration of immune cells to portal tracts. High-dose IgG significantly decreased CD4(+) T cell production of interleukin (IL)-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha and CD8(+) T cell production of IFN-gamma, as well as increased levels of regulatory T cells.
CONCLUSION: High-dose IgG therapy in murine BA dramatically decreased Th1 cell-mediated inflammation and biliary obstruction. This study lends support for consideration of IVIg clinical trials in infants with BA, to diminish the progressive intrahepatic bile duct injury.

• 出版日期2014-7