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

AIM: To observe the possible effects of transforming growth factor (TGF) β1, 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 (CCI4) (2 ml-kg^-1) twice a week. Fibrosisintervention group was given IL-10 at a dose of 4 μg-kg^-1 20 minutes before CCI4 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-β1,TNF-α, IL-6 and IL-10 were determined by enzyme-linkedimmunosorbent assay (ELISA). The liver tissues were taken for routine histological examination. RESULTS: Hepatic fibrosis was developed with the injection of CCI4. Values of the circulating TGFβ, TNFα, IL-6 and IL-10 in the control group were 25.495.56 ng.L^-1, 15.18±3.83ng.L^-1, 63.64±13.03 ng.L-^1 and 132.90±12.13 ng.L^-1,respectively. Their levels in the CCI4-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 TGFβ1, TNFα and IL-6 during hepatic fibrogenesis. These changes were pardally reversed by simultaneous administration of IL-10. The histological parameters, characterized by CCl4-intoxificatJon,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: TGFβ1, TNFα and IL-6 may play important roles during CCI4-induced hepatic fibrogenesis, and IL-10 may counterbalance their effects.

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 (2ml·kg^(-1)),twice a week.Fibrogenesis group was injected intraperitoneally with 50% carbon tetrachloride (CCl_4) (2ml·kg^(-1)) twice a week.Fibrosis- intervention group was given IL-10 at a dose of 4μg·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.