title: Effects of cytokines on carbon tetrachloride-induced hepatic fibrogenesis in rats.
abstract: OBJECTIVE
  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 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  TGFbeta(1), TNFalpha and IL-6 may play important roles during CCl(4)-induced hepatic fibrogenesis, and IL-10 may counterbalance their effects.
authors.affiliation: Department of Gastroenterology, Renmin Hospital, Wuhan University Medical School, @uhan 43060, Hubei Province, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Jie-Ping
authors.initials: JP
authors.lastname: Yu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Huang
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Chen
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology; D002251:Carbon Tetrachloride; D016207:Cytokines / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000097:blood / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000097:blood / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D015850:Interleukin-6; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002251:Carbon Tetrachloride