title: High-dose IgG therapy mitigates bile duct-targeted inflammation and obstruction in a mouse model of biliary atresia.
abstract: BACKGROUND
  A proposed etiology of biliary atresia (BA) entails a 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)-γ, and tumor necrosis factor (TNF)-α and CD8(+) T cell production of IFN-γ, as well as increased levels of regulatory T cells.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado School of Medicine and the Digestive Health Institute, Children's Hospital Colorado (CHCO), Aurora, Colorado (CO).|Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition University of Colorado School of Medicine and the Digestive Health Institute, Children's Hospital Colorado (CHCO), Aurora, Colorado (CO).
authors.forename: Erika K
authors.initials: EK
authors.lastname: Fenner
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado School of Medicine and the Digestive Health Institute, Children's Hospital Colorado (CHCO), Aurora, Colorado (CO).
authors.forename: Juri
authors.initials: J
authors.lastname: Boguniewicz
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado School of Medicine and the Digestive Health Institute, Children's Hospital Colorado (CHCO), Aurora, Colorado (CO).
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Tucker
authors.affiliation: Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition University of Colorado School of Medicine and the Digestive Health Institute, Children's Hospital Colorado (CHCO), Aurora, Colorado (CO).
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sokol
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado School of Medicine and the Digestive Health Institute, Children's Hospital Colorado (CHCO), Aurora, Colorado (CO).|Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition University of Colorado School of Medicine and the Digestive Health Institute, Children's Hospital Colorado (CHCO), Aurora, Colorado (CO).
authors.forename: Cara L
authors.initials: CL
authors.lastname: Mack
mesh_terms: D000418:Albumins / Q000627:therapeutic use; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects* / Q000473:pathology; D001656:Biliary Atresia / Q000276:immunology* / Q000628:therapy*; D001663:Bilirubin / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007249:Inflammation / Q000628:therapy*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D012401:Rotavirus; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000418:Albumins; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D007371:Interferon-gamma; D001663:Bilirubin
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