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

To observe the possible effects of transforming growth factor (TGF) beta(1), interleukin (IL)-6, tumor-necrosis factor (TNF) alpha and IL-10 on experimental rat hepatic fibrosis.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 microg/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-beta(1), TNF-alpha, IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). The liver tissues were taken for routine histological examination.Hepatic fibrosis was developed with the injection of CCl(4). Values of the circulating TGFbeta(1), TNFalpha, 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 TGFbeta(1), TNFalpha 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.TGFbeta(1), TNFalpha and IL-6 may play important roles during CCl(4)-induced hepatic fibrogenesis, and IL-10 may counterbalance their effects.