Antifibrotic effects of interleukin-10 on experimental hepatic fibrosis

Background/Aims: To study the effects of interleukin-10 on hepatic stellate cells and liver tissue in experimental rats hepatic fibrosis. Methodology: Rat hepatic fibrosis model induced by carbon tetrachloride was established. Liver tissues were harvested from the rats administered CCl4 with or without IL-10 treatment and the animals of the control group. The expression of TGF-beta(1), MMP2 and TIMP-1 in the liver tissues was measured by SP immunohistochemistry. In addition, another model was established; HSCs in rats in each group were isolated. RT-PCR was employed to analyze TGF-beta(1), MMP-2 and TIMP-1 mRNA expression in cells and immunocytochemistry was performed to detect protein expression of alpha-SAM, NF-kappa B, TGF-beta(1), MMP-2 and TIMP-1 in HSCs. Results: Rat hepatic fibrosis was developed successfully. The fibrosis changes were partially reversed by simultaneous administration of IL-10. The positive signals of TGF-beta(1), MMP-2 and TIMP-1 were observed more frequently (P < 0.05) in the CCl4-treated group compared to those in the IL-10-treated group and the control group. HSCs were successfully isolated. TGF-beta(1), MMP-2 and TIMP-1 mRNA in HSCs increased obviously during the course of hepatic fibrosis, and their levels were decreased after the treatment with IL-10 (P < 0.05). The immunocytochemistry positive levels for TGF-beta(1), MMP-2, TIMP-1, alpha-SMA and NF-kappa B in the fibrogenesis group were increased significantly compared to the normal group (P < 0.01). The positive signals decreased significantly (P < 0.05) after the treatment with IL-10. Conclusions: The expression of TGF-beta(1), MMP-2 and TIMP-1 increased in liver or in HSC of hepatic fibrosis rats and decreased after treatment with IL-10. The IL-10 could inhibit the activation of HSCs and make an antifibrogenic process come into effect in this way.