Effects of cytokines on carbon tetrachloride-induced hepatic fibrogenesis in rats

摘要

AIM: To observe the possible effects of transforming growth factor (TGF) β_1, interleukin (IL)-6, tumor-necrosis factor (TNF) α and IL-10 on experimental rat hepatic fibrosis. METHODS: One hundred SD rats were divided randomly into the three groups. Control group received intraperitoneal injection of saline (2 ml·kg~(-1)), twice a week. Fibrogenesis group was injected intraperitoneally with 50% carbon tetrachloride (CCl_4) (2 ml·kg~(-1)) twice a week. Fibrosis-intervention group was given IL-10 at a dose of 4 μg·kg~(-1) 20 minutes before CCl_4 administration from the third week. At the fifth, seventh, and ninth weeks, 7 to 10 rats in each group were sacrificed to collect serum. Levels of TGF-β_1, TNF-α, IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). The liver tissues were taken for routine histological examination. RESULTS: Hepatic fibrosis was developed with the injection of CCl_4. Values of the circulating TGFβ_1, TNFα, IL-6 and IL-10 in the control group were 25.49+-5.56 ng·L~(-1), 15.18+-3.83 ng·L~(-1), 63.64+-13.03 ng·L~(-1) and 132.90+-12.13 ng·L~(-1), respectively. Their levels in the CCl_4-intoxication group were 31.13+-6.41 ng·L~(-1), 18.91+-5.31 ng·L~(-1), 89.08+-25.39 ng·L~(-1) and 57.63+-18.88 ng·L~(-1), respectively, and those in the IL-10-intervention group were 26.11+-5.32 ng·L~(-1), 13.99+-1.86 ng·L~(-1), 74.71+-21.15 ng·L~(-1) and 88.19+-20.81 ng·L~(-1), respectively. A gradual increase was observed in the levels of TGFβ_1, TNFα and IL-6 during hepatic fibrogenesis. These changes were partially reversed by simultaneous administration of IL-10. The histological parameters, characterized by CCl_4-intoxification, also seemed to be improved with IL-10 treatment, the collagen production was reduced at the ninth week and the histological activity index was decreased from 7.9+-1.2 to 4.7+-0.9. CONCLUSION: TGFβ_1, TNFα and IL-6 may play important roles during CCl_4-induced hepatic fibrogenesis, and IL-10 may counterbalance their effects.