To Investigate The Role Mechanism Of IL-18Treatment Of Hepatocellular Carcinoma

Objective: To investigate of IL-18in the treatment of liver cancer and PD-1,Treg and Th17interrelationships and immune regulation.Method: SMMC7721human hepatoma cells were inoculated subcutaneouslyinto nude mice cells. After tumor formation, The20mice were randomly dividedinto two groups, The nude mice of Experimental group received intraperitoneallyinjected IL-18treatment every day and control group mice daily injections of saline,continuous treatment for30days. At the end of30consecutive days after treatment,all nude mice were killed and their tumor were taken and kept for further test. Theexpression and distribution of Th17、Treg and PD-1in SMMC7721cells weredetected by SP Immunohistochemistry in treatment group and control group. IL-17,IL-23, IL-10, TGF-β1and IFN-γ expression by ELISA treatment group and controlgroup mice serum or tissue homogenates. At the same time,IL-17, IL-23, IL-10,TGF-β and IFN-γ in treatment group and control group mice serum and tissuehomogenates were quantitatively detected by ELISA.Results:1. To observe PD-1and FOXP3in the experimental group and thecontrol group by Immunohistochemical technique: PD-1immunoreactivity wasmainly located in the membrane or cytosol, PD-1in the control group wassignificantly higher than in the experimental group by Semi-quantitative scoring, thedifference was statistically significant （P<0.01）. FOXP3immunoreactivity wasmainly located in the nucleus, FOXP3in the control group was significantly higherthan in the experimental group by Semi-quantitative scoring, the difference wasstatistically significant.2.To compared the nude serum levels of IL-10in experimentalgroup and the control group and normal group: concentrations were（64.27±21.32）pg/ml，（309.09±278.65） pg/ml，（36.56±26.54）pg/ml, there was a significantdifference among the three groups（P＜0.05）.The differences in the control group andthe normal group was statistically significant by pairwise comparison among the three groups（P＜0.05）.3. The nude serum levels of IFN-γ in experimental group and thecontrol group and normal group were compared: concentrations were（144.01±28.67）pg/ml，（57.31±2.18）pg/ml，（104.173±50.73）pg/ml, there was a significant differenceamong the three groups（P＜0.05）.And the experimental group and the control groupdifferences was statistically significant（P＜0.01）.4.The levels of IFN-γ from nudexenograft tissue homogenates in experimental group and the control group werecompared: concentrations were（463.88±264.02）pg/ml、（891.89±179.78）pg/ml, thedifferences was statistically significant（P＜0.05）.5. To observe IL-17in theexperimental group and the control group by Immunohistochemical technique: IL-17immunoreactivity was mainly located in the cytosol, IL-17in the experimental groupwas significantly higher than in the control group by Semi-quantitative scoring, thedifference was statistically significant (P <0.05).6. The nude serum levels of IL-17inexperimental group and the control group and normal group were compared:concentrations were（306.72±47.81）pg/ml、（171.59±23.18） pg/ml、（141.51±60.20）pg/ml, there was a significant difference among the three groups（P＜0.01）. Theexperimental group and the control group differences was statistically significant bypairwise comparison among the three groups（P＜0.05）,also in the control group andnormal group（P＜0.05）.Conclusion: IL-18maybe upregulate the cytokine IFN-γ, IL-17and IL-23, andinhibit the production of TGF-β1and IL-10, and reverse the negative regulation ofPD-1and Treg, and upregulate the expression of Th17to realization of anti-tumoreffect.