BACKGROUND: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex dise...BACKGROUND: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex diseases such as cancer. The distribution of interleukin-10 (IL-10) promoter polymorphisms in Chinese Han ethnic patients with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) was investigated in this study. METHODS: The polymorphisms of IL-10 promoter region were detected by pulymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing. Sixty-six health controls, 42 patients with HBV infection, 30 HCC patients, and cell line SMMC-7721 were examined this way. RESULTS: Polyrnorphisms of T/C or T/N on-872 site occurred frequently in Han ethnic population. Pulyrnorphisms were detected in HBV and HCC patients and cell line SMMC-7721. The hotspot among the pulymorphisms was inserting base A between-1058 and-1057. CONCLUSION: Polymorphisms of IL-10 promoter in HBV and HCC patients may be associated with HBV infection and HCC development.展开更多
AIM To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus(HCV) infection(OCI).METHODS One hundred and three cases of seronegative OCI and 155...AIM To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus(HCV) infection(OCI).METHODS One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection(CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28 B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system.RESULTS CXCL10 rs1439490 G/G was more prevalent in OCI patients(n = 93/103; 90.3%) than in CHC patients(n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients(192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28 B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peginterferon treatment than CHC patients(P < 0.05) and serum CXCL10 decreased significantly(P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection(OR = 0.31, 95%CI: 0.15-0.66, P = 0.002).CONCLUSION CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.展开更多
The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are reviewed.RBV up-regulate...The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are reviewed.RBV up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 dominance.Examination of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 production.The effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead box-P3.These findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected hepatocytes.Although an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV.展开更多
According to the important roles played by cytokines in induction of appropriate immune responses against hepatitis B virus(HBV),Dimitropoulou et al have examined the important cytokines in their patients.They showed ...According to the important roles played by cytokines in induction of appropriate immune responses against hepatitis B virus(HBV),Dimitropoulou et al have examined the important cytokines in their patients.They showed that the serum levels of interleukin 10(IL-10)and interferon-γ(IFN-γ)were decreased in patients with HBeAg-negative chronic active hepatitis B compared with the inactive hepatitis B virus carriers(Dimitropoulou et al 2013).The controversy can be considered regarding the decreased serum levels of IFN-γin the HBeAg-negative chronic active hepatitis B patients.They concluded that subsequent to decreased expression of IFN-γ,the process of HBV proliferation led to liver diseases.Previous studies stated that HBV is not directly cytopathic for the infected hepatocytes and immune responses are the main reason for destruction of hepatocytes(Chisari et al,2010).Scientists believe that immune responses against HBV are stronger in active forms of chronic HBV infected patients than inactive forms(Zhang et al,2012).Therefore,the findings from Dimitropoulou et al may deserve further attention and discussion.Additionally,downregulation of IL-10 inchronically active hepatitis B infected patients has also confirmed our claim.IL-10 is an anti-inflammatory cytokine and its expression is increased in inactive forms in order to downregulate immune responses(Arababadi et al,2012).Thus,based on the results from Dimitropoulou et al,it can be concluded that increased immune responses in chronically active hepatitis B infected patients are related to declined expression of IL-10 and interestingly IFN-γis not involved in induction of immune responses in these patients.展开更多
Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas(s Fas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role...Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas(s Fas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role in the development of chronic HBV infection.Methods Total of 90 cases with chronic HBV infection were randomly selected, including 10 of asymptomatic carriers(ASC), 28 of chronic hepatitis B(CHB), 26 of liver cirrhosis(LC) and 26 patients of hepatocellular carcinoma(HCC). Their clinical data and blood samples were collected, and serum was prepared and stored at-73℃. Anti-HBx was detected with an indirect ELISA established in our earlier research, and levels of IL-10, IL-12 and Fas were determined with commercial double-antibody sandwich ELISA kits. The mutual relationship between anti-HBx and IL-10, IL-12 or s Fas in serum were analyzed with the software SPSS 20.0. Results All levels of IL-10, IL-12 and s Fas in peripheral blood showed a rising trend with development of chronic HBV infection. The levels of IL-10 in ASC, CHB, LC and HCC groups were 13.93 ± 14.40 ng/L, 39.38 ± 20.77 ng/L, 69.06 ± 46.37 ng/L and 62.82 ± 23.42 ng/L, respectively, levels of IL-12 in the 4 groups were 15.64 ± 23.04 ng/L, 68.50 ± 23.14 ng/L, 76.83 ± 12.82 ng/L and 83.74 ± 24.88 ng/L, respectively, and levels of s Fas were 58.17 ± 77.42 ng/L, 179.88 ± 104.36 ng/L, 249.22 ± 107.80 ng/L and 252.98 ± 87.65 ng/L, respectively. Twenty-seven out of 90 patients showed a positive result for anti-HBx detection, including 1 in ASC, 4 in CHB, 12 in LC and 10 in HCC group. The levels of IL-10, IL-12 and sF as were higher in anti-HBx positive group than in negative group. Statistical analysis demonstrated significant differences of IL-10 and IL-12 between the two groups(P < 0.05), but the differences of s Fas had no statistical significance(P = 0.094). Conclusions Anti-HBx antibody is not protective, and is closely related to IL-10, IL-12 and s Fas. It may be an important serum indicator for aggravation from chronic hepatitis B to liver cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.展开更多
AIM： To study the mechanisms of hyporesponsiveness of HBV-specific CD4^＋ T cells by testing TH1 and TH2 commitment and regulatory T cells. METHODS： Nine patients with chronic hepatitis B were enrolled. Peripheral b...AIM： To study the mechanisms of hyporesponsiveness of HBV-specific CD4^＋ T cells by testing TH1 and TH2 commitment and regulatory T cells. METHODS： Nine patients with chronic hepatitis B were enrolled. Peripheral blood mononuclear cells were stimulated with HBcAg or HBsAg to evaluate their potential to commit to TH1 and TH2 differentiation. HBcAg-specific activity of regulatory T cells was evaluated by staining with antibodies to CD4, CD25, CTLA-4 and interleukin-10. The role of regulatory T cells was further assessed by treatment with anti-interleukin-10 antibody and depletion of CD4^＋CD25^＋ cells. RESULTS： Level of mRNAs for T-bet, IL-12R β2 and IL-4 was significantly lower in the patients than in healthy subjects with HBcAg stimulation. Although populations of CD4^＋CD25^highCTLA-4^＋ T cells were not different between the patients and healthy subjects, IL-10 secreting cells were found in CD4^＋ cells and CD4^＋CD25^＋ cells in the patients in response to HBcAg, and they were not found in cells which were stimulated with HBsAg. Addition of anti-IL-10 antibody recovered the amount of HBcAgspecific TH1 antibody compared with control antibody （P 〈 0.01, 0.34% ± 0.12% vs 0.15% ± 0.04%）. Deletion of CD4^＋CD25^＋ T cells increased the amount of HBcAgspecific TH1 antibody when compared with lymphoo/tes reconstituted using regulatory T cells （P 〈 0.01, 0.03% ± 0.02% vs 0.18% ± 0.05%）.CONCLUSION： The results indicate that the mechanism of T cell hyporesponsiveness to HBcAg includes activation of HBcAg-induced regulatory T cells in contrast to an increase in TH2-committed cells in response to HBsAg.展开更多
目的探讨慢性乙型肝炎病毒（hepatitis B virus,HBV）感染的不同临床类型患者白细胞介素2（IL-2）、白细胞介素10（IL-10）水平的变化及其意义。方法采用ELISA法检测91例慢性HBV感染患者[慢性重型乙型肝炎（慢重肝组,SH）18例,乙型肝炎...目的探讨慢性乙型肝炎病毒（hepatitis B virus,HBV）感染的不同临床类型患者白细胞介素2（IL-2）、白细胞介素10（IL-10）水平的变化及其意义。方法采用ELISA法检测91例慢性HBV感染患者[慢性重型乙型肝炎（慢重肝组,SH）18例,乙型肝炎肝硬化（肝硬化组,LC）25例,慢性乙型肝炎（慢乙肝组,CB）48例（其中重度17例、中度21例、轻度10例）]血清IL-2、IL-10的水平。应用SPSS 13.0 for window统计软件对3组慢性HBV感染不同临床类型患者IL-2、IL-10水平进行比较分析。结果慢重肝组血清IL-2、IL-10水平与肝硬化组比较,差异均无统计学意义（均P〉0.05）;慢重肝组与肝硬化组血清IL-2、IL-10的95%可信区间（95%CI）分别为：-36.88－33.72、-67.00-95.14。慢重肝组血清IL-2水平与慢乙肝组比较,差异无统计学意义（P〉0.05）;而血清IL-10水平与慢乙肝组比较,差异有统计学意义（P〈0.05）。慢重肝组与慢乙肝组血清IL-2、IL-10的95%CI分别为：-13.52-50.42、22.59-169.43。肝硬化组血清IL-2水平与慢乙肝组比较,差异无统计学意义（P〉0.05）;而血清IL-10水平与慢乙肝组比较,差异有统计学意义（P〈0.05）。肝硬化组与慢乙肝组血清IL-2、IL-10的95%CI分别为：-7.98-48.05、17.61-146.27。结论IL-2对慢性HBV感染的临床类型影响不大。而IL-10可能对慢性HBV感染的临床类型有影响,且血清IL-10水平的升高在炎症损伤反应中起到重要的作用。展开更多
文摘BACKGROUND: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex diseases such as cancer. The distribution of interleukin-10 (IL-10) promoter polymorphisms in Chinese Han ethnic patients with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) was investigated in this study. METHODS: The polymorphisms of IL-10 promoter region were detected by pulymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing. Sixty-six health controls, 42 patients with HBV infection, 30 HCC patients, and cell line SMMC-7721 were examined this way. RESULTS: Polyrnorphisms of T/C or T/N on-872 site occurred frequently in Han ethnic population. Pulyrnorphisms were detected in HBV and HCC patients and cell line SMMC-7721. The hotspot among the pulymorphisms was inserting base A between-1058 and-1057. CONCLUSION: Polymorphisms of IL-10 promoter in HBV and HCC patients may be associated with HBV infection and HCC development.
基金Supported by the National Natural Science Foundation of China,No.81670533the Jilin Provincial Science&Technology Department,No.2013 0102088JCthe Jilin Provincial Development and Reform Commission,No.2013C028-3
文摘AIM To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus(HCV) infection(OCI).METHODS One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection(CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28 B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system.RESULTS CXCL10 rs1439490 G/G was more prevalent in OCI patients(n = 93/103; 90.3%) than in CHC patients(n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients(192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28 B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peginterferon treatment than CHC patients(P < 0.05) and serum CXCL10 decreased significantly(P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection(OR = 0.31, 95%CI: 0.15-0.66, P = 0.002).CONCLUSION CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.
文摘The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are reviewed.RBV up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 dominance.Examination of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 production.The effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead box-P3.These findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected hepatocytes.Although an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV.
文摘According to the important roles played by cytokines in induction of appropriate immune responses against hepatitis B virus(HBV),Dimitropoulou et al have examined the important cytokines in their patients.They showed that the serum levels of interleukin 10(IL-10)and interferon-γ(IFN-γ)were decreased in patients with HBeAg-negative chronic active hepatitis B compared with the inactive hepatitis B virus carriers(Dimitropoulou et al 2013).The controversy can be considered regarding the decreased serum levels of IFN-γin the HBeAg-negative chronic active hepatitis B patients.They concluded that subsequent to decreased expression of IFN-γ,the process of HBV proliferation led to liver diseases.Previous studies stated that HBV is not directly cytopathic for the infected hepatocytes and immune responses are the main reason for destruction of hepatocytes(Chisari et al,2010).Scientists believe that immune responses against HBV are stronger in active forms of chronic HBV infected patients than inactive forms(Zhang et al,2012).Therefore,the findings from Dimitropoulou et al may deserve further attention and discussion.Additionally,downregulation of IL-10 inchronically active hepatitis B infected patients has also confirmed our claim.IL-10 is an anti-inflammatory cytokine and its expression is increased in inactive forms in order to downregulate immune responses(Arababadi et al,2012).Thus,based on the results from Dimitropoulou et al,it can be concluded that increased immune responses in chronically active hepatitis B infected patients are related to declined expression of IL-10 and interestingly IFN-γis not involved in induction of immune responses in these patients.
基金Jinan Bureau of Science and Technology(No.200807033-1)
文摘Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas(s Fas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role in the development of chronic HBV infection.Methods Total of 90 cases with chronic HBV infection were randomly selected, including 10 of asymptomatic carriers(ASC), 28 of chronic hepatitis B(CHB), 26 of liver cirrhosis(LC) and 26 patients of hepatocellular carcinoma(HCC). Their clinical data and blood samples were collected, and serum was prepared and stored at-73℃. Anti-HBx was detected with an indirect ELISA established in our earlier research, and levels of IL-10, IL-12 and Fas were determined with commercial double-antibody sandwich ELISA kits. The mutual relationship between anti-HBx and IL-10, IL-12 or s Fas in serum were analyzed with the software SPSS 20.0. Results All levels of IL-10, IL-12 and s Fas in peripheral blood showed a rising trend with development of chronic HBV infection. The levels of IL-10 in ASC, CHB, LC and HCC groups were 13.93 ± 14.40 ng/L, 39.38 ± 20.77 ng/L, 69.06 ± 46.37 ng/L and 62.82 ± 23.42 ng/L, respectively, levels of IL-12 in the 4 groups were 15.64 ± 23.04 ng/L, 68.50 ± 23.14 ng/L, 76.83 ± 12.82 ng/L and 83.74 ± 24.88 ng/L, respectively, and levels of s Fas were 58.17 ± 77.42 ng/L, 179.88 ± 104.36 ng/L, 249.22 ± 107.80 ng/L and 252.98 ± 87.65 ng/L, respectively. Twenty-seven out of 90 patients showed a positive result for anti-HBx detection, including 1 in ASC, 4 in CHB, 12 in LC and 10 in HCC group. The levels of IL-10, IL-12 and sF as were higher in anti-HBx positive group than in negative group. Statistical analysis demonstrated significant differences of IL-10 and IL-12 between the two groups(P < 0.05), but the differences of s Fas had no statistical significance(P = 0.094). Conclusions Anti-HBx antibody is not protective, and is closely related to IL-10, IL-12 and s Fas. It may be an important serum indicator for aggravation from chronic hepatitis B to liver cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.
基金Supported by Grant from Ministry of Education, Culture, Sports, Science and Technology of Japan, No. 12877084
文摘AIM： To study the mechanisms of hyporesponsiveness of HBV-specific CD4^＋ T cells by testing TH1 and TH2 commitment and regulatory T cells. METHODS： Nine patients with chronic hepatitis B were enrolled. Peripheral blood mononuclear cells were stimulated with HBcAg or HBsAg to evaluate their potential to commit to TH1 and TH2 differentiation. HBcAg-specific activity of regulatory T cells was evaluated by staining with antibodies to CD4, CD25, CTLA-4 and interleukin-10. The role of regulatory T cells was further assessed by treatment with anti-interleukin-10 antibody and depletion of CD4^＋CD25^＋ cells. RESULTS： Level of mRNAs for T-bet, IL-12R β2 and IL-4 was significantly lower in the patients than in healthy subjects with HBcAg stimulation. Although populations of CD4^＋CD25^highCTLA-4^＋ T cells were not different between the patients and healthy subjects, IL-10 secreting cells were found in CD4^＋ cells and CD4^＋CD25^＋ cells in the patients in response to HBcAg, and they were not found in cells which were stimulated with HBsAg. Addition of anti-IL-10 antibody recovered the amount of HBcAgspecific TH1 antibody compared with control antibody （P 〈 0.01, 0.34% ± 0.12% vs 0.15% ± 0.04%）. Deletion of CD4^＋CD25^＋ T cells increased the amount of HBcAgspecific TH1 antibody when compared with lymphoo/tes reconstituted using regulatory T cells （P 〈 0.01, 0.03% ± 0.02% vs 0.18% ± 0.05%）.CONCLUSION： The results indicate that the mechanism of T cell hyporesponsiveness to HBcAg includes activation of HBcAg-induced regulatory T cells in contrast to an increase in TH2-committed cells in response to HBsAg.
文摘目的探讨慢性乙型肝炎病毒（hepatitis B virus,HBV）感染的不同临床类型患者白细胞介素2（IL-2）、白细胞介素10（IL-10）水平的变化及其意义。方法采用ELISA法检测91例慢性HBV感染患者[慢性重型乙型肝炎（慢重肝组,SH）18例,乙型肝炎肝硬化（肝硬化组,LC）25例,慢性乙型肝炎（慢乙肝组,CB）48例（其中重度17例、中度21例、轻度10例）]血清IL-2、IL-10的水平。应用SPSS 13.0 for window统计软件对3组慢性HBV感染不同临床类型患者IL-2、IL-10水平进行比较分析。结果慢重肝组血清IL-2、IL-10水平与肝硬化组比较,差异均无统计学意义（均P〉0.05）;慢重肝组与肝硬化组血清IL-2、IL-10的95%可信区间（95%CI）分别为：-36.88－33.72、-67.00-95.14。慢重肝组血清IL-2水平与慢乙肝组比较,差异无统计学意义（P〉0.05）;而血清IL-10水平与慢乙肝组比较,差异有统计学意义（P〈0.05）。慢重肝组与慢乙肝组血清IL-2、IL-10的95%CI分别为：-13.52-50.42、22.59-169.43。肝硬化组血清IL-2水平与慢乙肝组比较,差异无统计学意义（P〉0.05）;而血清IL-10水平与慢乙肝组比较,差异有统计学意义（P〈0.05）。肝硬化组与慢乙肝组血清IL-2、IL-10的95%CI分别为：-7.98-48.05、17.61-146.27。结论IL-2对慢性HBV感染的临床类型影响不大。而IL-10可能对慢性HBV感染的临床类型有影响,且血清IL-10水平的升高在炎症损伤反应中起到重要的作用。
