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 inves tigated in;he 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 facto r-alpha (TNF-alpha) and serum levels of transforming growth factor-beta 1 ( TGF-beta 1) increased and were significantly higher in IL-10 KO mice, where as IL-6 serum levels were only slightly increased compared with WT mice. At histological! examination, the livers disclosed a significantly more promi nent neutrophilic infiltration in IL-10 KO mice 12 and 24 hours after CCl4 injection. In contrast, hepatocyte necrosis, evaluated by histological exam ination and serum alanine aminotransferase levels, was only marginally affe cted. The proliferative response of hepatocytes, assessed by the proliferat ing cell nuclear-antigen labeling index, was significantly increased in IL- 10 KO mice, compared with WT mice 48 hours after CCl4 injection. Finally, r epeated CCl4 injections led to more liver fibrosis in IL-IO KO mice after 7 weeks. In conclusion, endogenous IL-10 marginally affects the hepatocyte n ecrosis although it controls the acute inflammatory burst induced by CCl4. During liver repair, it limits the proliferative response of hepatocytes an d the development of fibrosis.