Faculty Collaboration Database

High-dose IgG therapy mitigates bile duct-targeted inflammation and obstruction in a mouse model of biliary atresia. Pediatr Res 2014 Jul;76(1):72-80

Date

04/15/2014

Pubmed ID

24727948

Pubmed Central ID

PMC4062601

DOI

10.1038/pr.2014.46

Scopus ID

2-s2.0-84902688139 (requires institutional sign-in at Scopus site)   17 Citations

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.

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.

Author List

Fenner EK, Boguniewicz J, Tucker RM, Sokol RJ, Mack CL

Author

Cara Lynn Mack MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Albumins
Animals
Bile Ducts
Biliary Atresia
Bilirubin
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Disease Models, Animal
Immunoglobulin G
Immunoglobulins, Intravenous
Inflammation
Interferon-gamma
Interleukin-2
Mice
Rotavirus
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1