Study On Cytokine Tnf-α,il-1,il-6 And IL-8 In The Liver Of Guinea Pigs Sensitized By Trichloroethylene

OBJECTIVE Detected and compared the expression of TNF-α, IL-1, IL-6, IL-8 and IL-10 of different groups. Studied the role of these cytokines in liver injury of TCE sensitized Guinea Pigs and investigated the mechanism of liver injury of Dermatitis Medicamentosa-like of Trichloroethylene.METHODS Selected 45 white female guinea pigs,weight around 250g,then were randomly divided into blank control group, solvent control group, TCE treatment group. We used the GPMT method to set up the model,then TCE treatment group was divided into TCE sensitized-24h group,TCE sensitized-72h group,TCE unsensitized-24h group,TCE unsensitized-72h group based on the result of sensitization.We recorded the observations and took photos of the test areas.Gave every sample a mark according to the Tab1,and class the grade of each group according the Tab.2.Then suctioned the serum of Guinea Pigs and killed the animals,and then eviscerated the liver what was made to paraffin block and tissue homogenate.The expression of TNF-α,IL-1, IL-6, and IL-8 were tested by immunohistochemistry and ELISA. SPSS13.0 were used to analysis the results.RESULTS1.In skin sensitization test,there were no erythema or edema in the blank group and solvent control group;19 of 30 animals in TCE treatment group appeared erythema,the rate was 63.3%.2.Liver function The ALT and AST levels of TCE sensitized groups were highter than solvent control(p<0.05);Compared with TCE sensitized 24h group and TCE14d group,the ALT and AST levels of TCE sensitized 72h group were elevated(p<0.05); Compared with solvent control,the ALB levels of TCE sensitized 72h group were declined(p<0.05).3. Pathological observation Guinea pig liver cells of blank control group and solvent control group were arranged in neat,uniform cytoplasm,large round nuclei,prominent nucleoli,nuclear membrane clearly;TCE unsensitized group had no obvious abnormalities;Cell swelling was observed in a few of liver cells of TCE sensitized 24h group;more liver cells can be observed edema in TCE sensitized 72h group and a few of liver cells nucleu brocken away.4. The leve of TNF-α,IL-1,IL-6,IL-84.1The results of TNF-αThe result of IH:The TNF-αlevels of TCE14d group,TCE sensitized 24h group,TCE sensitized 72h group were higher than solvent control(p<0.05);TCE sensitized group were higher than unsensitized groups(p<0.05); TCE sensitized 72h group were higher than TCE sensitized 24h group(p<0.05).The result of ELISA:The TNF-αlevels of TCE unsensitized 24h group, TCE sensitized 24h group,TCE unsensitized 72h group and TCE sensitized 72h group were higher than solvent control(p<0.05);TCE sensitized 24h group,TCE sensitized 72h group were higher than unsensitized groups (p <0.05);TCE sensitized 72h group and TCE sensitized 24h group were higher than TCE14d group (p <0.05).4.2The results of IL-1 The result of IH: The IL-1 levels of TCE treatment groups were higher than the solvent control (p<0.05);TCE sensitized group TCE were higher than TCE unsensitized group(p<0.05);TCE sensitized 24h group,TCE sensitized 72h group were higher than TCE14d group (p <0.05);TCE sensitized 72h group were higher than TCE sensitized 24h group.The result of ELISA:The IL-1 levels of TCE treatment groups were higher than the solvent control (p<0.05);TCE sensitized 72h group were higher than TCE unsensitized 72h group(p<0.05);The IL-1 levels of TCE sensitized 72h group were higher than TCE sensitized 24h group and TCE14d group (p <0.05).4.3 The results of IL-6 The result of IH: The IL-6 levels of TCE sensitized 24h group and TCE sensitized 72h group were highter than solvent control(p<0.05);TCE sensitized group were higher than TCE unsensitized group(p<0.05);TCE sensitized 24h group and TCE sensitized 72h group were higher than T14d(p<0.05).The result of ELISA:The IL-6 levels of TCE sensitized 24h group,TCE unsensitized 72h group and TCE sensitized 72h group were highter than solvent control group(p<0.05);TCE sensitized 72h group were higher than TCE unsensitized 72h group and TCE14d grou (p<0.05).4.4 The results of IL-8 The result of IH: The IL-8 levels of TCE sensitized 24h group and TCE sensitized 72h group were higher than solvent control group(p<0.05);TCE sensitized group were higher than TCE unsensitized group(p<0.05);TCE sensitized 24h group and TCE sensitized 72h group were higher than T14d(p<0.05).The result of ELISA:Compared with solvent control group,the IL-8 levels of TCE treatment groups were elevated (p <0.05);TCE sensitized 72h group were higher than TCE unsensitized 72h group and TCE14d grou (p<0.05).5. TNF-αwere significantly correlated with IL-1,IL-6,IL-8;IL-1 were significantly correlated with IL-6,IL-8;ALT and AST was positively correlated with TNF-αand IL-6(p<0.05);Except TNF-α, IL-1,IL -6 and IL-8 were not significantly correlated with ALB.CONCLUSIONS This study demonstrated that TCE not only can cause hypersensitivity in guinea pigs,but also can cause liver damage in varying degrees of TCE sensitized Guinea pigs;Liver damage was observed in sensitized guinea pigs and TNF-α,IL-1,IL-6,IL-8 levels in liver of TCE sensitized Guinea pigs were higher than the other groups,ALT and AST were significant correlated with TNF-αand IL-6,suggest that TNF-α,IL-1,IL-6,IL-8 play an important role in liver injury of Guinea pigs induced by TCE.