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

AIM: 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. 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 intra peritoneally with 50% carbon tetrachloride (CCl4) (2 ml.kg-1) twice a week. Fibrosis-intervention group was given IL-10 at a dose of 4 mug.kg(-1) 20 minutes before CCl4 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. RESULTS: Hepatic fibrosis was developed with the injection Of CCl4. 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 CCl4-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 CCl4-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: TGFbeta(1), TNFalpha and IL-6 may play important roles during CCl4-induced hepatic fibrogenesis, and IL-10 may counterbalance their effects.