| Objectives： The immune response is critically important for the Chronichepatitis B virus infection pathogenesis. The function and role of the CD4+CD25+regulatory T cells in HBV infection is increasingly becoming theresearch focus in recent years. Making sure the regulating mechanism of theCD4~+CD25~+regulatory T cells on the effect T cells and related cytokines inimmune tolerance state is of great significance for the treatment of effectivelyterminate persistent infection. FoxP~3is widely recognized as the most specifictranscription factor of CD4~+CD25~+regulatory T cells, and the CD4~+CD25~+regulatory T cell activity level can be accurately reflected by detecting theFoxp3mRNA expression. In this study, the changes and the significance ofFoxP~3mRNA expression, serum IL-12, IL-18in patients with Hepatitis BCirrhosis will be preliminarily investigated, and the relationships betweenFoxP~3mRNA and IL-12or IL-18, the relationships between viral loads andFoxP~3mRNA or IL-12or IL-18will be analyzed.Methods：1.The total RNAs of the persons in the healthy control group,chronic hepatitis B group and liver cirrhosis group were extracted and then tobe reversely transcripted into cDNA. Subsequently the Foxp3mRNAexpressions were be measured with Real-Time quantitative PCR (Real-TimePCR) amplification. The relationship between FoxP~3mRNAs and viral loadswere analyzed.2. The serum IL-12, IL-18contents in the healthy control group,chronic hepatitis B group and liver cirrhosis group were tested by ELISA, andthe relationship with the viral loads and IL-12or IL-18were analyzed.3. TheFoxP~3mRNA expression and IL-12, IL-18levels in the healthy control group, chronic hepatitis B group, cirrhosis group were compared each other, and therelations between them were analyzed.4. the ALT, AST, ALB, PTA, HBsAg,HBsAb, HBeAg, HBeAb, HBcAb and HBV-DNA load in the healthy controlgroup, chronic hepatitis B group and liver cirrhosis group were tested andanalyzed.Results：1. The Foxp3mRNA expression levels and IL-12, IL-18contents inthe chronic hepatitis group and in the liver cirrhosis group were significantlyand statistically higher than those in the healthy control group (P <0.05).2.Further paired comparisons showed: The difference of FoxP~3mRNA betweenthe control group and the cirrhosis group, between the healthy control groupand the chronic hepatitis B group was significant (Mann-Whitney U value of0.000, p <0.05); The difference of FoxP~3mRNA between the chronic hepatitisB group and the liver cirrhosis group was not statistically significant(Mann-Whitney U value of225.500, p=0.189). The difference of IL-12between the control group and the liver cirrhosis group significantly different(Mann-Whitney U value of24.000, p <0.05); The difference of IL-12between the control group and the chronic hepatitis B group was significantlydifferent (Mann-Whitney U value of12.000, p <0.05); The difference ofIL-12between the chronic hepatitis B group and the liver cirrhosis group wasnot statistically significant (Mann-Whitney U value of264.000p 0.05). Thedifference of IL-18between the control group and the liver cirrhosis groupsignificantly different (Mann-Whitney U value of7.000, p <0.05); Thedifference of IL-18between the control group and the chronic hepatitis B groupwas significantly different (Mann-Whitney U value of36.000, p <0.05); Thedifference of IL-18between the chronic hepatitis B group and the liver cirrhosisgroup was not statistically significant (Mann-Whitney U value of223.000,p 0.05).3. Being analyzedby Spearman correlation coefficient method forChronic Hepatitis B, there is not a correlation between FoxP~3mRNA and IL-12(r=-0.297, P=0.059) or between Foxp3mRNA and IL-18(r=-0.242, P= 0.078).4. Also being analyzed by Spearman correlation coefficient method forChronic Hepatitis B, there is a positive correlation between IL-12and IL-18(r=0.828，p=0.000).5. Also being analyzed by Spearman correlation coefficientmethod for Chronic Hepatitis B, there is a positive correlation betweenHBV-DNA and IL-18FoxP~3mRNA (r=0.830，P=0.031); there is a negativecorrelation between HBV-DNA and IL-12(r=-0.459，P=0.000); there is anegative correlation between HBV-DNA and IL-18(r=-0.328，P=0.015). Thesedata mean that HBV-DNA showed a downward trend along with increasingIL-12and IL-18.Conclusion:1. Showed in this research, the Foxp3mRNA levels in thechronic hepatitis B group and in the liver cirrhotic were higher than thehealthy control group (P <0.05), and there is a positive correlation betweenthe HBV-DNA loads and the Foxp3mRNAs. This showed that theabnormal elevated FoxP~3mRNA (representing CD4~+CD25~+Treg cells)inhibited the effective T cells and subsequently reduced the body’s immuneresponse and induced an immune tolerance, so that the HBV could not beeliminated and caused continued HBV infection, and resulted in the viralhepatitis developing chronically. The mechanism maybe the cytokinesproduced during the inflammatory reaction in the patients with chronicviral hepatitis stimulated the proliferation of the Treg cells, resulting thehigher expression of Foxp3mRNA.2. The abnormally increased IL-12and IL-18in the serum of the patients with chronic hepatitis B may be theresult of the unbalance of Th1/Th2cells, and play roles in the process ofchronic hepatitis B, involved in the process of viral hepatitis, liver cirrhosis and liver inflammatory injury.3. In patients with chronichepatitis B or liver cirrhosis, the viral loads and serum cytokines IL-12orIL-18are negative correlated, the higher the IL-12or IL-18, the lower theviral loads. The enhanced cell-mediated immunity is beneficial for viralclearance, and the dominant Th1cells enhanced CD8+T cells will furtheraggravate the damage to the liver cells. thus, IL-12, IL-18participate in theprocess of the body’s immune clearance of HBV.4. In this research, nocorrelation between FoxP~3mRNA and IL-12or IL-18was observed, sofurther research should be implemented. |
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