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

AIM:To observe the possible effects of transforming growthfactor (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 randomlyinto the three groups.Control group received intraperitonealinjection of saline (2ml·kg-1),twice a week.Fibrogenesisgroup was injected intraperitoneally with 50% carbontetrachloride (CCl4) (2ml·kg-1) twice a week.Fibrosis-intervention group was given IL-10 at a dose of 4μg·kg-120 minutes before CCl4administration from the third week.At the fifth,seventh,and ninth weeks,7 to 10 rats in eachgroup 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 takenfor routine histological examination.RESULTS:Hepatic fibrosis was developed with the injectionof CCl4.Values of the circulating TGFβ1,TNFα,IL-6 and IL-10 in the control group were 25.49±5.56 ng·L-1,15.18±3.83ng·L-1,63.64±13.03 ng·L-1and 132.90±12.13 ng·L-1,respectively.Their levels in the CCl4-intoxication group were31.13±6.41 ng·L-1,18.91±5.31 ng·L-1,89.08±25.39 ng·L-1and57.63±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-1and 88.19±20.81 ng·L-1,respectively.Agradual increase was observed in the levels of TGFβ1,TNFαand IL-6 during hepatic fibrogenesis.These changes werepartially reversed by simultaneous administration of IL-10.Thehistological parameters,characterized by CCl4-intoxification,also seemed to be improved with IL-10 treatment,the collagenproduction was reduced at the ninth week and the histologicalactivity index was decreased from 7.9±1.2 to 4.7±0.9.CONCLUSION:TGFβ1,TNFα and IL-6 may play importantroles during CCl4-induced hepatic fibrogenesis,and IL-10may counterbalance their effects.