Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice.
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-) and serum levels of transforming growth factor-beta 1 (TGF-beta1) 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.
Louis
H
H
Department of Gastroenterology and Hepatopancreatology, Brussels, Belgium.
Van Laethem
J L
JL
Wu
W
W
Quertinmont
E
E
Degraef
C
C
Van den Berg
K
K
Demols
A
A
Goldman
M
M
Le Moine
O
O
Geerts
A
A
Devière
J
J
D000818:Animals; D002251:Carbon Tetrachloride; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D007267:Injections; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008099:Liver / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009336:Necrosis; D009504:Neutrophils / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002251:Carbon Tetrachloride