Infliximab and Dexamethasone Attenuate the Ductular Reaction in Mice.
Chronic hepatic injury is accompanied by a ductular response that is strongly correlated with disease severity and progression of fibrosis. To investigate whether anti-inflammatory drugs can modulate the ductular response, we treated mice suffering from a steatotic or cholestatic injury with anti-TNF-α antibodies (Infliximab) or glucocorticoids (Dexamethasone). We discovered that Dexamethasone and Infliximab can both modulate the adaptive remodeling of the biliary architecture that occurs upon liver injury and limit extracellular matrix deposition. Infliximab treatment, at least in these steatotic and cholestatic mouse models, is the safer approach since it does not increase liver injury, allows inflammation to take place but inhibits efficiently the ductular response and extracellular matrix deposition. Infliximab-based therapy could, thus, still be of importance in multiple chronic liver disorders that display a ductular response such as alcoholic liver disease or sclerosing cholangitis.
Laboratory of Liver Cell Biology, Vrije Universiteit Brussel (VUB), Belgium.
Stefaan
S
Verhulst
Laboratory of Liver Cell Biology, Vrije Universiteit Brussel (VUB), Belgium.|Department of Gastroenterology and Hepatology, University Duisburg-Essen, Germany.
Jan
J
Best
Section of Gastroenterology, Ralph H Johnson VAMC, Charleston, SC, USA.|Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, USA.
Wing-Kin
WK
Syn
Laboratory of Liver Cell Biology, Vrije Universiteit Brussel (VUB), Belgium.
Hendrik
H
Reynaert
Unit Diabetes Pathology and Therapy, VUB, Brussel, Belgium.
Karine H
KH
Hellemans
Department of Gastroenterology and Hepatology, University Duisburg-Essen, Germany.
Ali
A
Canbay
Laboratory of Liver Cell Biology, Vrije Universiteit Brussel (VUB), Belgium.
Laurent
L
Dolle
Laboratory of Liver Cell Biology, Vrije Universiteit Brussel (VUB), Belgium.
Leo A
LA
van Grunsven
D000818:Animals; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology; D002779:Cholestasis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000069285:Infliximab / Q000494:pharmacology*; D008297:Male; D051379:Mice
D003907:Dexamethasone; D000069285:Infliximab