Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice
Hubert Louis
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Hubert Louis, Jean-Luc Van Laethem, and Olivier Le Moine have been research fellows of the Fondation Erasme.
Search for more papers by this authorJean-Luc Van Laethem
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorWei Wu
Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorEric Quertinmont
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorChantal Degraef
Laboratory of Experimental Cytology and Cancerology, Brussels, Belgium
Search for more papers by this authorKit Van den Berg
Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorAnne Demols
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorMichel Goldman
Department of Immunology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorOlivier Le Moine
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorAlbert Geerts
Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorCorresponding Author
Jacques Devière M.D.
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Department of Gastroenterology, Hôpital Erasme, 808 route de Lennik, B 1070 Brussels, Belgium. Fax: 32-2-555-46-97===Search for more papers by this authorHubert Louis
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Hubert Louis, Jean-Luc Van Laethem, and Olivier Le Moine have been research fellows of the Fondation Erasme.
Search for more papers by this authorJean-Luc Van Laethem
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorWei Wu
Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorEric Quertinmont
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorChantal Degraef
Laboratory of Experimental Cytology and Cancerology, Brussels, Belgium
Search for more papers by this authorKit Van den Berg
Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorAnne Demols
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorMichel Goldman
Department of Immunology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Search for more papers by this authorOlivier Le Moine
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Search for more papers by this authorAlbert Geerts
Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorCorresponding Author
Jacques Devière M.D.
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium
Laboratory of Experimental Gastroenterology, Brussels, Belgium
Department of Gastroenterology, Hôpital Erasme, 808 route de Lennik, B 1070 Brussels, Belgium. Fax: 32-2-555-46-97===Search for more papers by this authorAbstract
The role of the anti-inflammatory cytokine interleukin-10 (IL-10) was investigated in the mouse model of liver injury induced by carbon tetrachloride (CCl4). To address the role of endogenous IL-10 production, acute hepatitis was induced by CCl4 in C57Bl/6 IL-10 gene knock out (KO) and wild-type (WT) mice. After CCl4 challenge, serum and liver levels of tumor necrosis factor-alpha (TNF-α) and serum levels of transforming growth factor-beta 1 (TGF-β1) increased and were significantly higher in IL-10 KO mice, whereas IL-6 serum levels were only slightly increased compared with WT mice. At histological examination, the livers disclosed a significantly more prominent neutrophilic infiltration in IL-10 KO mice 12 and 24 hours after CCl4 injection. In contrast, hepatocyte necrosis, evaluated by histological examination and serum alanine aminotransferase levels, was only marginally affected. The proliferative response of hepatocytes, assessed by the proliferating cell nuclear-antigen labeling index, was significantly increased in IL-10 KO mice, compared with WT mice 48 hours after CCl4 injection. Finally, repeated CCl4 injections led to more liver fibrosis in IL-10 KO mice after 7 weeks. In conclusion, endogenous IL-10 marginally affects the hepatocyte necrosis although it controls the acute inflammatory burst induced by CCl4. During liver repair, it limits the proliferative response of hepatocytes and the development of fibrosis.
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