Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

mIL-2R,T cell subsets & hepatitis C

AIM: To study the levels of membrane interleukin-2 receptor (mIL-2R) and T cell subsets in peripheral blood mononuclear cells (PBMC) from patients with hepatitis C and their role in the pathogenesis of hepatitis C. METHODS: The levels of mIL-2R and T cells subsets in PBMC were detected by biotin- streptatividin (BSA) technique before and after stimulation with PHA in 203 patients with hepatitis C with HCV-RNA(+), anti-HCV(+), anti-HCV(-). RESULTS: The total expressive levels of mIL-2R before and after stimulation with PHA(0.03+/-0.01, 0.03+/-0.02, 0.04+/-0.02, 0.36+/-0.03), and T cell subsets in PBMC (0.62+/-0.06, 0.37+/-0.05, 0.35+/-0.07) were all lower in patients with hepatitis C than those in normal controls (0.66+/-0.07, 0.41+/-0.06, 0.31+/-0.05, P【0.01). Among the patients, the levels of mIL-2R were lower in silence than those in situation of PHA inducting (P【0.01). However, the levels of mIL-2R were similar in acute hepatitis C to that in chronic hepatitis C (P】0.05). The levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+) were lower and CD(8)(+) was higher in patients with acute and chronic hepatitis C with anti-HCV(+) than those in normal controls (0.62+/-0.06, 0.37+/-0.05, 0.35+/-0.07, 1.18+/-0.30, 0.61+/-0.07, 0.37+/-0.05, 1.39+/-0.33, 0.31+/-0.05, P【0.05-P【0.01). CONCLUSION: The cellular immunity is obviously changed in patients with hepatitis C. The levels of mIL-2R and activation of T cells are closely associated with chronicity of hepatitis C.

血清可溶性白介素-2受体测定在丙型肝炎及干扰素治疗中的意义

采用ELISA法测定了60例丙型肝炎患者血清sIL-2R水平。结果显示,丙型肝炎患者血清sIL-2R水平明显高于正常对照组(P<0.01),急性肝炎高于慢性肝炎(P<0.01)。肝功能损害程度与血清sIL-2R水平呈正相关(r=0.57,P<0.01)。29例HCV-RNA阳性患者应用α-2b干扰素治疗,治疗后血清sIL-2R较治疗前明显下降(P<0.05),其中17例HCV-RNA阴转,阴转组较未阴转组下降明显(P<0.05)。结果提示:血清sIL-2R水平与丙型肝炎患者肝细胞病变程度有关,同时对观察干扰素的疗效亦有所帮助。

丙型肝炎患者外周血T淋巴细胞亚群及sIL-2R变化的研究

目的 探讨丙型肝炎患者外周血T淋巴细胞亚群及可溶性白细胞介素 2受体的变化。方法 以输血后丙型肝炎为研究对象 ,以健康体检者为对照 ,分别检测其外周血T淋巴细胞亚群及可溶性白细胞介素 2受体 ,对部分患者进行α -干扰素抗病毒治疗 ,并于治疗前后观察此两项指标的变化 ,检测方法分别用双抗夹心ELISA法和流式细胞仪。结果 丙型肝炎患者血清可溶性白细胞介素 2受体明显高于正常对照组 ,与血清ALT呈正相关 ;各型肝炎时 ,CD4+ T细胞及CD4+ 与CD8+ T细胞比值均下降 ,CD8+ T细胞升高 ;α -干扰素抗病毒治疗后 ,病毒复制指标阴转 ,同时可溶性白细胞介素 2受体水平下降 ,细胞免疫功能改善。结论 免疫反应参与丙型肝炎发病 ,各型丙型肝炎患者均有不同程度的免疫功能紊乱 ,观察T淋巴细胞亚群及可溶性白细胞介素 2受体的变化 ,对判断丙型肝炎转归和预后有重要的参考价值。

乙型肝炎后肝硬化患者外周血IL-2、IFN-γ活性与肝功能分级的关系

目的：探讨乙型肝炎后肝硬化（ＰＨＣ）患者外周血白介素２（ＩＬ２）和γ干扰素（ＩＦＮγ）活性与肝功能状态的关系。方法：测定５６例ＰＨＣ患者和２４例健康成人外周血淋巴细胞ＩＬ２受体（ＩＬ２Ｒ）的表达，ＩＬ２和ＩＦＮγ生成及血清可溶性ＩＬ２受体（ｓＩＬ２Ｒ）。结果：ＰＨＣ组和对照组的ＩＬ２活性与ＩＬ２Ｒ表达率、ＩＦＮγ活性之间均呈正相关，与ｓＩＬ２Ｒ水平则负相关。与对照组比较，ＰＨＣ组ＩＬ２Ｒ表达，ＩＬ２和ＩＦＮγ生成均显著低下（Ｐ＜０．０５、＜０．０１、＜０．００１），而ｓＩＬ２Ｒ水平则显著升高（Ｐ＜０．００１）；而且随着ＣｈｉｌｄＰｕｇｈ肝功能分级之降低，上述这种改变亦明显。结论：ＰＨＣ患者存在一定程度的Ｔ细胞功能障碍与缺陷。

慢性乙肝患者抗病毒治疗血清IL-10、IL-12、sIL-2R、TNF水平变化的临床观察

目的 探讨IL 10、IL 12、sIL 2R、TNF在慢性乙型肝炎发病中的作用 ,观察IFN抗病毒治疗对于上述因子水平的影响。方法 ELISA法检测 14例正常人及 30例慢性肝炎患者 (包括IFN治疗前后 )血清中上述细胞因子水平。结果 慢性肝炎患者血清中上述细胞因子水平显著高于正常对照组 (P <0 .0 5 ) ,且其值与ALT显著正相关 ;经IFN治疗后上述因子水平均明显降低 ,抗病毒无效组治疗前血清中sIL 2R、IL 10水平明显高于有效组 (P <0 .0 5 )。结论 上述因子共同参与了慢性乙型肝炎的发病 ,并可用于评价IFN对于机体免疫状态的影响 ;且sIL 2R、IL 10对预测抗病毒疗效有重要意义。

聚乙二醇干扰素联合胸腺肽肠溶片对慢性肝炎患者CXCR3、CCR6及血清IL-2及其可溶性配体水平的影响

目的 分析聚乙二醇干扰素联合胸腺肽肠溶片对慢性肝炎患者外周血CXCR3、CCR6、白细胞介素-2（IL-2）及其可溶性配体水平的影响。方法 选取2015年6月~2016年6月于衢州市人民医院感染科治疗的慢性乙型肝炎患者125例,随机分为观察组62例和对照组63例。观察组给予聚乙二醇干扰素联合胸腺肽肠溶片治疗,对照组给予胸腺肽肠溶片治疗,流式细胞仪法检测患者患者T细胞CXCR3、CCR6表达,采用酶联免疫吸附法检测患者血液中IL-2及可溶性白细胞介素-2受体（sIL-2R）的水平,并对比2组患者治疗效果。结果 治疗后,观察组IL-2、s IL-2R分别为（16.4±5.6）、（9.4±2.1）,明显低于对照组,而CXCR3为（5.81±0.9）、CCR6为（5.54±1.2）,明显高于对照组,差异有统计学意义（P〈0.05）;观察组HBsAg、HBeAg、HBV-DNA分别为（1.5±0.4）、（1.6±0.9）、（1.6±0.3）,明显低于对照组,差异有统计学意义（P〈0.05）,观察组ALT、AST、TBIL、IBIL分别为（34.5±8.7）、（31.4±6.9）、（14.6±6.9）、（9.4±2.9）,明显低于对照组,差异有统计学意义（P〈0.05）。结论 干扰素联合胸腺肽肠溶片治疗慢性乙型肝炎有助于提高患者趋化因子受体水平、抑制炎症反应程度,有助于改善乙型肝炎患者肝功能、抑制病毒复制,比单用胸腺肽肠溶片治疗慢性肝炎的效果更好。

丙型肝炎患者外周血单核细胞中IFNAR2 mRNA表达的研究

目的探究丙型肝炎病毒(HCV)不同感染阶段,外周血单核细胞(PBMC)干扰素α/β受体2(IFNAR2)mRNA表达水平,并研究其与干扰素(IFN)疗效的关系。方法 58例丙肝抗体阳性患者,根据临床表现分为3组:急性肝炎组(4例),慢性肝炎组(46例),肝硬化组(8例)。15名健康志愿者作为对照组。应用密度梯度离心法将外周血单核细胞分离,应用RT PCR扩增IFNAR2 mRNA。结果 58例丙型肝炎患PBMC IFNAR2 mRNA检出率为87.9%,而对照组为33.3%,差异具有统计学意义(P<0.05);慢性丙型肝炎组较肝硬化组检出率高(93.5%和50%,P<0.05),2组间PBMC HCV RNA的阳性率无差别(P>0.05)。PBMC IFNAR2 mRNA水平与干扰素疗效相关(P<0.05)。结论丙型肝炎病毒感染可上调PBMC IFNAR2 mRNA的表达,慢性丙型肝炎患者PBMC IFNAR2 mRNA表达高于肝硬化患者,其表达可能与病毒载量无关,而与干扰素疗效相关。

IFN-α1b治疗对慢性乙肝患者血清IL-1、sIL-2R和IFN-γ水平的影响

目的 探讨α 干扰素 (INF α 1b)治疗慢性乙型肝炎细胞免疫机制。方法 收集IFN α 1b治疗慢性乙型肝炎患者 3 0例 ,分别在治疗前、治疗后 1个月、3个月、6个月和 9个月留取血清标本 ,用MTT法检测血清白细胞介素 1(IL 1)水平 ,用ELISA法检测血清可溶性白细胞介素 2受体 (sIL 2R)和γ 干扰素 (INF γ)水平 ,并与 3 0例健康献血员作对照。结果 与正常对照组相比 ,慢性乙型肝炎患者血清sIL 2R水平升高 (P <0 0 5 ) ,经IFN α治疗后 ,血清IL 1、sIL 2R明显升高 (P <0 0 1)。结论 IFN α 1b调节体内细胞因子变化 ,参与细胞免疫调节。

α-干扰素治疗慢性乙型肝炎抗病毒疗效与血清IL-2、sIL-2R变化关系

目的 :观察慢性乙型肝炎 (CHB)患者经 α-干扰素 (IFN- α)抗病毒治疗前后血清中白细胞介素 - 2 (IL- 2 )和可溶性白细胞介素 - 2受体 (s IL- 2 R)水平的变化与乙肝病毒消长之间的关系。方法 :收集治疗前后血清标本 - 2 0℃保存 ,通过 EL ISA法同步检测并与正常人作对照。结果 :IFN- α无效应答组 (n=15 )治疗前血清中 IL- 2水平较有效应答组 (n=10 )和正常组 (n=10 )高 (P<0 .0 1) ;但治疗后则明显下降 ,而有效应答组治疗后则明显升高 ;s IL- 2 R血清水平在 IFN- α有效应答组治疗前明显高于无效应答组和正常组 (P<0 .0 1) ,但治疗后则明显下降 ,虽然无效应答组治疗后略有上升 ,但治疗前后无显著性差异。结论 :IFN- α除本身对 CHB患者体内病毒复制有抑制作用外 ,还可能参与体内免疫调节 ,对病毒复制产生影响。

T helper cells in patients with chronic hepatitis B virus infection

OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transform growth factor-beta (TGF-beta) in single CD4(+) T cells isolated from peripheral blood mononuclear cells (PBMCs) and the role of polarized Th cell populations in chronic HBV-infection was discussed. METHODS: PBMCs from chronically infected HBV individuals were isolated, stimulated by PMA/Ionomycin/Monensin, and IL-4, IFN-gamma and TGF-beta production by CD4(+) T cells was determined by using fluorescence activated cell sorter (FACS) analysis. RESULTS: The percentage of IFN-gamma-producing T cells, IL-4-producing T cells and TGF-beta-producing T cells ranged from 2.3% - 18.6%, 1.1% - 8.7% and 0.7% - 7.1% respectively in CD4(+) T cells from non-infected individuals. Most of CD4(+) T cells from PBMCs in chronically infected HBV individuals were Th0 cells. The proportion of Th1 cells increased significantly with hepatic inflammatory activity, and in the active period of chronic hepatitis B infection were higher than those in the non-active period (P 0.05), but were higher than that from controls (P

胸腺肽肠溶片联合聚乙二醇干扰素对慢性肝炎患者的治疗效果及其相关指标的影响

目的探讨胸腺肽肠溶片联合聚乙二醇干扰素对慢性肝炎患者血清中CXC趋化因子受体3(CXCR3)、趋化因子受体6(CCR6)、血清白介素2(IL-2)、肝功能指标及其可溶性配体水平的影响。方法选取2017年9月~2018年9月我院接收的74例慢性肝炎患者,根据随机数字表法分为观察组与对照组,每组各37例。对照组仅接受胸腺肽肠溶片治疗,观察组接受胸腺肽肠溶片联合聚乙二醇干扰素治疗。比较两组患者治疗后的CXCR3、CCR6、清蛋白(ALB)、总胆红素(TBil)、丙氨酸氨基转移酶(ALT)、乙肝病毒脱氧核糖核酸(HBV-DNA)、乙肝表面抗原(HBsAg)、乙型肝炎E抗原(HBeAg)等病毒学指标水平。结果观察组患者治疗后的CXCR3、CCR6高于对照组,血清IL-2水平低于对照组;观察组患者治疗后的ALB水平高于对照组,TBil、ALT水平均低于对照组;观察组患者治疗后的HBV-DNA、HBsAg、HBeAg水平低于对照组,差异均有统计学意义(P<0.05)。结论慢性肝炎患者经胸腺肽肠溶片联合聚乙二醇干扰素治疗后,CXCR3、CCR6及血清IL-2水平可以有效降低,且肝功能及其可溶性配体水平显著改善,治疗效果确切。

Preliminary Study on Efficacy of Oxymatrine in Treatment of Patients with Chronic Hepatitis C

Objective: To evaluate the efficacy of oxymatrine in the treatment of chronic hepatitis C and todiscuss its mechanism. Methods: Forty-three patients with chronic HCV infection were randomly divided intothe treated group (20 cases) and the control group (23 cases). The treated group was given oxymatrine 600 mgper day intramuscularly for three months, and the control group was given the general liver protective agentssuch as vitamins. Serum HCV-RNA, alanine aminotransferase (ALT), soluble interleukin--2 receptor and collagen type tV (IV-C) were determined before and after treatment. Results: Eight out of 17 HCV-RNA-positive(47. 1 % ) in the treated group converted to HCV-RNA-negative cases, while in 18 cases of the control group,the negative convertion only took place in 1 patient (5. 6% ), the negative conversion rate was significantlyhigher in the treated group than that in the control group (P < 0. 05). The normalization rates of serum ALT ofthe treated group at the end of the first and second month treatment were higher than those of the controlgroup, but after three months treatment, the normalization rates of the two groups were not different significantly. BOth serum levels of IV-C and plasma levels of soluble interleukin-2 receptor were significantly reducedafter oxymatrine treatment for three months (P < 0. 05). Conclusion: Oxymatrine is effective on eliminatingHCV-RNA and reducing fibrosis activity, so it could be a safe, effective drug in the treatment of chronic hepatitis C.Keywods: oxymatrine; hepatitis C virus ribonucleic acid; soluble interleukin-2 receptor; collagen typeⅢ

α-干扰素和香菇多糖对乙型肝炎病毒感染者白细胞介素-2受体表达的影响

测定了21例慢性乙型肝炎患者外周血单个核细胞(PBMC)白细胞介素-2受体(Tac 蛋白)表达水平及20例慢性乙型肝炎患者血清可溶性白细胞介素-2受体(sIL-2R)水平,发现与正常人组相比,患者 Tac 蛋白表达水平明显减低(P<0.01),血清 sIL-2R 明显增高(P<0.01)。体内、体外试验结果表明,α-干扰素有明显的增强患者 PBMC Tac 蛋白表达的作用,促患者抗 HBe 阳转及 HBV DNA 阴转,且血清sIL-2R 降低。而香菇多糖组无此变化,推测患者 Tac 蛋白表达的增强及血清 sIL-2R的减少,可能与α-干扰素对患者体内 HBV DNA 复制的抑制作用有关。

慢性乙型肝炎患者应用拉米夫定前后T淋巴细胞亚群、CD4^＋CD25^＋调节性T淋巴细胞及白细胞介素-10、干扰素-γ的变化

目的观察慢性乙型肝炎（CHB）患者应用拉米夫定抗病毒治疗前后外周血T淋巴细胞亚群、CD4^＋CD25^＋调节性T淋巴细胞（CD4^＋CD25^＋Treg）及IL-10、IFN-γ水平的变化。方法选择CHB患者90例，在应用拉米夫定抗病毒治疗前及治疗后52周时，用流式细胞仪检测患者外周血T淋巴细胞亚群；在治疗前及治疗后12、24、36、52周时，用流式细胞仪检测外周血CD4^＋CD25^＋Treg频率，用双抗体夹心ELISA法检测IL-10、IFN-γ水平。组间及组内总体均数比较采用方差齐性的单因素方差分析或Dunnett’s检验，组内治疗前后两时段均数比较采用配对t检验。结果在90例CHB患者中，完全应答的32例患者的CD4^＋T淋巴细胞、CD8^＋T淋巴细胞及CD4^＋／CD8^＋。较治疗前升高（t=4．055、3．267、2．328，均P〈0．05），外周血CD4^＋CD25^＋Treg频率在0、12、24、36、52周时分别为（5．40±0．60）％、（4．99±0．59）％、（4．54±0．72）％、（3．86±0．95）％、（3．44±0．76）％；IFN-γ水平、IFN-γ／IL-10逐步上升，IL-10水平逐步下降。部分应答的43例患者的CD4^＋T淋巴细胞及CD4^＋／CD8^＋较治疗前升高（t=3．484、2．018，均P〈0．05），CD8^＋T淋巴细胞较治疗前无明显差异，外周血CD4^＋CD25^＋Treg频率在0、12、24、36、52周时分别为（5．65±0．60）％、（5．23±0．63）％、（4．65±0．98）％、（4．42±0．97）％、（4．32±0．82）％，IFN-γ水平、IFN—γ／IL-10升高，IL-10水平降低。无应答的15例患者的外周血CD4^＋T淋巴细胞、CD8^＋T淋巴细胞及CD4^＋／CD8^＋、外周血CD4^＋CD25^＋Treg频率及IFN-γ水平、IFN-y／IL-10、IL-10水平较治疗前无明显变化。结论应用拉米夫定治疗过程中，获得满意应答的CHB患者的外周血CD4^＋CD25^＋Treg频率下降，CD4^＋／CD8^＋、IFN-γ／IL-10的比例升高。