Co-delivery of ccl19 gene enhances anti-caries DNA vaccine pCIA-P immunogenicity in mice by increasing dendritic cell migration to secondary lymphoid tissues

Aim:

To investigate how co-delivery of the gene encoding C–C chemokine ligand-19 (CCL-19) affected the systemic immune responses to an anti-caries DNA vaccine pCIA-P in mice.

Methods:

Plasmid encoding CCL19-GFP fusion protein (pCCL19/GFP) was constructed by inserting murine ccl19 gene into GFP-expressing vector pAcGFP1-N1. Chemotactic effect of the fusion protein on murine dendritic cells (DCs) was assessed in vitro and in vivo using transwell and flow cytometric analysis, respectively. BALB/c mice were administered anti-caries DNA vaccine pCIA-P plus pCCL19/GFP (each 100 μg, im) or pCIA-P alone. Serum level of anti-PAc IgG was assessed with ELISA. Splenocytes from the mice were stimulated with PAc protein for 48 h, and IFN-γ and IL-4 production was measured with ELISA. The presence of pCCL19/GFP in spleen and draining lymph nodes was assessed using PCR. The expression of pCCL19/GFP protein in these tissues was analyzed under microscope and with flow cytometry.

Results:

The expression level of CCL19-GFP fusion protein was considerably increased 48 h after transfection of COS-7 cells with pCCL19/GFP plasmids. The fusion protein showed potent chemotactic activity on DCs in vitro. The level of serum PAc-specific IgG was significantly increased from 4 to 14 weeks in the mice vaccinated with pCIA-P plus pCCL19/GFP. Compared to mice vaccinated with pCIA-P alone, the splenocytes from mice vaccinated with pCIA-P plus pCCL19/GFP produced significantly higher level of IFN-γ, but IL-4 production had no significant change. Following intromuscular co-delivery, pCCL19/GFP plasmid and fusion protein were detected in the spleen and draining lymph nodes. Administration of CCL19 gene in mice markedly increased the number of mature DCs in secondary lymphoid tissues.

Conclusion:

CCL19 serves as an effective adjuvant for anti-caries DNA vaccine by inducing chemotactic migration of DCs to secondary lymphoid tissues.     

Good Manufacturing Practices production and analysis of a DNA vaccine against dental caries

Aim:

To prepare a clinical-grade anti-caries DNA vaccine pGJA-P/VAX and explore its immune effect and protective efficacy against a cariogenic bacterial challenge.

Methods:

A large-scale industrial production process was developed under Good Manufacturing Practices (GMP) by combining and optimizing common unit operations such as alkaline lysis, precipitation, endotoxin removal and column chromatography. Quality controls of the purified bulk and final lyophilized vaccine were conducted according to authoritative guidelines. Mice and gnotobiotic rats were intranasally immunized with clinical-grade pGJA-P/VAX with chitosan. Antibody levels of serum IgG and salivary SIgA were assessed by an enzyme-linked immunosorbent assay (ELISA), and caries activity was evaluated by the Keyes method. pGJA-P/VAX and pVAX1 prepared by a laboratory-scale commercial kit were used as controls.

Results:

The production process proved to be scalable and reproducible. Impurities including host protein, residual RNA, genomic DNA and endotoxin in the purified plasmid were all under the limits of set specifications. Intranasal vaccination with clinical-grade pGJA-P/VAX induced higher serum IgG and salivary SIgA in both mice and gnotobiotic rats. While in the experimental caries model, the enamel (E), dentinal slight (Ds), and dentinal moderate (Dm) caries lesions were reduced by 21.1%, 33.0%, and 40.9%, respectively.

Conclusion:

The production process under GMP was efficient in preparing clinical-grade pGJA-P/VAX with high purity and intended effectiveness, thus facilitating future clinical trials for the anti-caries DNA vaccine.     

Enhanced efficacy of CTLA-4 fusion anti-caries DNA vaccines in gnotobiotic hamsters

Aim： To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T-lymphocyte-associated antigen 4 （CTLA-4） fusion anti-caries DNA vaccines pGJA-P/VAX1, pGJA-P, and non-fusion anti-caries DNA construct pGLUA-P in hamsters. In addition, the ability of CTLA-4 to target pGJA-P/ VAXl-encoding antigen to dendritic cells was tested in vitro. Methods： All DNA constructs contain genes encoding the A-P regions of a cell surface protein （PAc） and the glucan binding （GLU） domain of glucosyltransferases （GTFs） of cariogenic organism Streptococcus mutans. Human dendritic cells were mixed with the CTLA-4-Ig-GLU-A-P protein expressed by pGJA-P/VAX 1-transfected cells and analyzed by flow cytometry. Gnotobiotic hamsters were immunized with anticaries DNA vaccines by intramuscular injection or intranasal administration. Antibody responses to a representative antigen PAc were assayed by ELISA, and caries protection was evaluated by Keyes caries scores. Results： A flow cytometric analysis demonstrated that CTLA-4-Ig-GLU-A-P protein was capable of binding to human dendritic cells, pGJA-P/VAX1 and pGJA-P induced significantly higher specific salivary and serum anti-PAc antibody responses than pGLUA-P. Significantly fewer caries lesions were also observed in hamsters immunized with pGJA-P/VAX1 and pGJA-P. There was no significant difference in the anti-PAc antibody level or caries scores between pGJA-P/VAX1 and pGJA-P-immunized groups. Conclusion： Antigen encoded by CTLA-4 fusion anti-caries DNA vaccine pGJA-P/VAX1 could specifically bind to human dendritic cells through the interaction of CTLA-4 and B7 molecules. Fusing antigen to CTLA-4 has been proven to greatly enhance the immunogenicity and protective efficacy of anticaries DNA vaccines.     

新型表位基因疫苗的构建及对小鼠黑色素瘤的影响

目的：构建以MAGE-1（161—169）为表位的癌症基因疫苗并检测其抗小鼠黑色素瘤效果。方法：构建基因疫苗pcDNA—HSP70-MAGE—l（161-169）,并免疫C57BL／6小鼠。最后一次免疫后第2周,接种小鼠黑色素瘤细胞。于肿瘤细胞接种后14d,处死全部动物,称量肿瘤的重量。采用ELISA法对小鼠血清中抗MAGE-1-IgG类抗体及小鼠原代脾淋巴细胞IFN-7释放水平进行检测。结果：pcDNA-HSP70-MAGE-1（161—169）表位基因疫苗能够成功地诱发机体产生抗MAGE-1的特异性抗体,并能在体内起到抗小鼠黑色素瘤作用,抑瘤率为40．7％。同时还能提高约3．05倍的小鼠原代脾淋巴细胞IFN-7释放量。结论：pcDNA-HSP70-MAGE-1（161-169）有望成为有效的抗小鼠黑色素瘤基因疫苗。     

Electroporation-mediated gene therapy

Non-viral gene transfer is markedly enhanced by the application of in vivo electroporation. Electroporation is a safe and efficient system to introduce genes to a wide variety of tissues, including skeletal muscle, tumors, kidney, liver and skin. Electroporation has been demonstrated to be effective in numerous disease models. This review focuses on the principles of electroporation and the target tissues employed for gene therapy. Based on the accumulation of positive results, the first clinical study for the treatment of malignant melanoma is now underway, and preclinical studies have suggested that electroporation is useful as a gene therapy protocol.     

Protective efficacy of Psidium cattleianum and Myracrodruon urundeuva aqueous extracts against caries development in rats

This study evaluated the influence of Psidium cattleianum Sabine (Myrtaceae) and Myracrodruon urundeuva Allemão (Anacardiaceae) aqueous extracts on S. mutans counts and dental enamel micro-hardness of rats submitted to a cariogenic challenge. Sixty Wistar rats were distributed in three groups and received water (control) or aqueous extracts of Psidium cattleianum or Myracrodruon urundeuva as hydration solution. Initially the animals had their sublingual and submandibular salivary glands surgically removed and the parotid ducts ligated. Then the rats were inoculated with 10⁶ CFU of Streptococcus mutans ATCC 35668 and were fed with a cariogenic diet. To detect and quantify the presence of S. mutans, oral biofilms were sampled and microbial DNA was extracted and submitted to amplification by means of real-time PCR (Polymerase Chain Reaction). After seven weeks the animals were sacrificed and enamel demineralization was analyzed by cross-sectional micro-hardness. Both extracts produced a significant reduction on S. mutans counts and decreased the enamel demineralization. It can be concluded that the extracts tested had a significant effect on S. mutans in oral biofilm of the rats, decreasing S. mutans accumulation and enamel demineralization.     

Inhibition of biofilm formation and antibacterial properties of a silver nano-coating on human dentine

The survival of pathogenic bacteria in the oral cavity depends on their successful adhesion to dental surfaces and their ability to develop into biofilms, known as dental plaque. Bacteria from the dental plaque are responsible for the development of dental caries, gingivitis, periodontitis, stomatitis and peri-implantitis. Certain metal nanoparticles have been suggested for infection control and the management of the oral biofilm. Here, it is shown that application of a silver nano-coating directly on dentine can successfully prevent the biofilm formation on dentine surfaces as well as inhibit bacterial growth in the surrounding media. This silver nano-coating was found to be stable (>98.8%) and to maintain its integrity in biological fluids. Its antibacterial activity was compared to silver nitrate and the widely used clinical antiseptic, chlorhexidine. The bacterial growth and cell viability were quantitatively assessed by measuring the turbidity, proportion of live and dead cells and lactate production. All three bioassays showed that silver nanoparticles and silver nitrate dentine coatings were equally highly bactericidal (>99.5%), while inhibiting bacterial adhesion. However, the latter caused significant dentine discolouration (ΔE* = 50.3). The chlorhexidine coating showed no antibacterial effect. Thus, silver nanoparticles may be a viable alternative to both chlorhexidine and silver nitrate, protecting from dental plaque and secondary caries when applied as a dentine coating, while they may provide the platform for creating anti-biofilm surfaces in medical devices and other biomedical applications.     

Anti-caries DNA vaccine-induced secretory immunoglobulin A antibodies inhibit formation of Streptococcus mutans biofilms in vitro

Aim:

To investigate the effects of anti-caries DNA vaccine-induced salivary secretory immunoglobulin A (S-IgA) antibodies on Streptococcus mutans (S. mutans) adherence and biofilms formation in vitro.

Methods:

Adult female Wistar rats were intranasally immunized with the anti-caries DNA vaccine pGJA-P/VAX. Their saliva samples were collected at different times after the immunization, and S-IgA antibody level in the saliva and its inhibition on S. mutans adherence were examined. The effects of S-IgA in the saliva with the strongest inhibitory effects were examined at 3 different stages, ie acquired pellicles, biofilm formation and production of mature biofilms. The number of viable bacteria and depth of the biofilm at 16 h in each stage were determined using counting colony forming units and using a confocal laser scanning microscopy (CLSM). The participation of S-IgA in acquired pellicles and its aggregation with S. mutans were also observed under CLSM.

Results:

The S-IgA titer in saliva reached its peak and exhibited the strongest inhibition on S. mutans adhesion at 10 weeks after the immunization. The colonies and depth of the biofilm in the saliva-pretreated group were 41.79% and 41.02%, respectively, less than the control group. The colonies and depth of the biofilm in the co-culture group were 27.4% and 22.81% less than the control group. The assembly of S. mutans and S-IgA was observed under CLSM after co-cultivation. In the mature-stage biofilm, no differences were observed between the different groups.

Conclusion:

These results demonstrate that the anti-caries DNA vaccine induces the production of specific S-IgA antibodies that may prevent dental caries by inhibiting the initial adherence of S. mutans onto tooth surfaces, thereby reducing the accumulation of S. mutans on the acquired pellicles.     

IL-10抑制脂多糖诱导的Hela细胞IL-15和IL-6转录

目的研究IL-10对脂多糖(LPS)诱导的Hela细胞IL-15mRNA和IL-6 mRNA表达的影响,分析其激活的信号转导通路。方法培养的Hela细胞,经不同浓度的LPS及IL-10单独或联合处理后,提取细胞总RNA和总蛋白,RT-PCR分析IL-15和IL-6转录水平的变化,Westernblot分析信号转导通路蛋白变化。结果RT-PCR分析得知①1ng～10μgLPS刺激Hela细胞12h后,IL-15 mRNA和IL-6 mRNA水平均明显上调(与对照组比较:P<0.01),且存在剂量依赖关系,100ng/mL时达峰值;100ng/mLLPS刺激Hela细胞0～24h,IL-15 mRNA和IL-6 mRNA水平亦明显上调(与对照组比较:P<0.01),24h内存在时间依赖关系,12h时达峰值。②单独IL-10(10ng/mL)作用于Hela细胞12h后,IL-15 mRNA和IL-6 mRNA没有明显变化(与对照组比较:P>0.05)。不同浓度的IL-10(1,10,100ng/mL)均下调100ng/mLLPS诱导的Hela细胞IL-15 mRNA和IL-6 mRNA的表达,且浓度越高IL-10抑制作用越明显。Western blot分析显示LPS主要通过磷酸化信号蛋白PI3K/AKT和ERK1/2上调IL-15和IL-6转录,IL-10能阻断AKT的磷酸化而对ERK1/2的磷酸化没有影响。结论IL-10可抑制LPS诱导的炎症细胞因子IL-15和IL-6的转录,这可能与其阻断AKT的磷酸化有关,因而,IL-10可能应用于某些临床感染性疾病的预防和治疗。     

Novel investigational drugs targeting IL-6 signaling for the treatment of depression

Introduction: Elevated levels of IL-6 have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). Convergent evidence suggests that IL-6 primarily mediates proinflammatory functions via the soluble IL-6 receptor/trans-signaling, and anti-inflammatory functions via a transmembrane receptor (IL-6R). A targeted approach to selectively inhibit IL-6 trans-signaling may offer putative antidepressant effects.

Areas covered: This review addresses three primary domains. The first focuses on the biological role of IL-6 within inflammation and its signal transduction pathways. The second addresses the potential contributions of IL-6 to the pathophysiology of MDD, and the mechanisms that may mediate these effects. Finally, the article outlines the therapeutic benefits of incorporating anti-inflammatory properties into the pharmacological treatment of MDD, and proposes inhibition of IL-6 signaling as a viable treatment strategy.

Expert opinion: To improve drug development for the treatment of MDD, there is a critical need to identify promising targets. Target identification will require guidance from a strategic framework such as The Research Domain Criteria, and convincing evidence relating known targets to brain function under both physiological and pathological conditions. Although current evidence provides rationale for administering anti-IL-6 treatments in MDD, further studies confirming safety, target affinity and therapeutic benefits are warranted.     

乙肝病毒感染者HBV-DNA与IL-1、IL-6的关系及临床意义

目的探讨乙肝病毒感染者血清IL-1及IL-6含量变化及其与乙肝病毒脱氧核糖核酸（HBV-DNA）载量的相关性,寻找HBV感染相关疾病的炎症活动指标。方法采用ELISA法检测慢性乙型肝炎（CHB）56例、乙肝后肝硬化（LC）38例、原发性肝细胞癌（PHC）40例及正常对照40例血清IL-1、IL-6水平;采用荧光定量聚合酶链反应（FQ-PCR）检测上述174例血清HBV-DNA。结果 CHB、LC及PHC患者血清IL-1、IL-6水平均显著高于对照组（P〈0.05）,但3组之间比较的差异无统计学意义;HBV-DNA阳性组和HBV-DNA阴性组IL-1、IL-6含量均显著高于对照组（P〈0.05）,且HBV-DNA阳性组显著高于HBV-DNA阴性组（P〈0.05）。结论乙肝病毒感染者存在免疫功能调节紊乱,IL-1、IL-6在其中起重要作用,且其与HBV-DNA载量呈正相关关系,可作为乙肝相关疾病炎症活动的观察指标。     

慢性肾炎治疗前后血清IL-2、IL-6、IL-10、IL-18和T淋巴细胞亚群检测意义

目的探讨慢性肾炎患者治疗前后血清IL-2、IL-6、IL-10、IL-18和T淋巴细胞亚群的变化。方法分别应用放免法、ELISA法和单克隆抗体法对30例慢性肾炎患者治疗前后进行了血清IL-2、IL-6、IL-10、IL-18和T淋巴细胞亚群水平的检测,并与35名正常健康人作比较。结果慢性肾炎患者在治疗前血清IL-2和CD4/CD8比值明显低于正常人组（P〈0.05）,而IL-6、IL-10和IL-18水平高于正常人组（P〈0.01）;经半年治疗后血清IL-2、IL-6、IL-10、IL-18和CD4/CD8与治疗前组比较差异有统计学意义（P〈0.05）。结论检测慢性肾炎患者血清IL-2、IL-6、IL-10、IL-18和T淋巴细胞亚群水平对判断病情及其预后均具有一定的临床实用价值。     

辛伐他汀对野百合碱诱导的肺动脉高压大鼠IL-6和IL-8表达的影响

目的观察辛伐他汀对野百合碱（MCT）诱导的肺动脉高压大鼠炎症细胞因子IL-6和IL-8表达的影响,探讨辛伐他汀作用于肺动脉高压的机制。方法将30只健康雄性SD大鼠随机平均分为正常对照组、MCT诱导的肺动脉高压组（模型对照组）、辛伐他汀干预治疗组（治疗组）。模型对照组和治疗组注射野百合碱造模。治疗21 d后,采用右心导管法检测大鼠平均肺动脉压（mPAP）;称量RV和LV＋S,计算右心肥大指数（RVHI）。采用RT-PCR检测大鼠肺组织中IL-6和IL-8 mRNA的表达,采用ELISA法检测大鼠血清中IL-6和IL-8水平。结果模型对照组mPAP和RVHI值显著高于治疗组和正常对照组,治疗组和正常对照组mPAP和RVHI值比较无显著性差异。模型对照组大鼠肺组织中IL-6和IL-8 mRNA的表达和血清中IL-6和IL-8水平显著高于正常对照组和治疗组,而治疗组大鼠肺组织中IL-6和IL-8 mRNA的表达和血清中IL-6水平与正常对照组比较无显著性差异,但治疗组大鼠血清IL-8水平高于正常对照组（P〈0.05）。结论辛伐他汀可通过抑制MCT诱导大鼠肺动脉高压模型大鼠肺组织中炎性细胞因子的表达、下调大鼠炎性细胞因子的分泌,达到对肺动脉高压的治疗作用。     

动态监测重症肺炎患者血液和支气管肺泡灌洗液中IL-6、IL-8、IL-10的含量及其意义

目的动态监测重症肺炎患者血液和支气管肺泡灌洗液中IL-6、IL-8、IL-10的浓度变化，探讨其临床意义。方法收住本院ICU的重症肺炎患者，人选患者在病程的第1天，CPIS评分〉6分为CPIS高分组，CPIS评分≤6分为CPIS低分组。在病程的第1、4、7天抽取外周静脉血做细胞因子测定以及支气管肺泡灌洗液检查。结果无论在血液中还是在BALF中，CPIS高分组的IL-6、IL-8水平比CPIS低分组明显增高，差异有统计学意义（P〈0．01），CPIS高分组IL．10水平比CPIS低分组组稍高，但尚未达显著差异；血液和BALF中IL石、IL-8水平与CPIS评分呈正相关（P〈0．05），血液和BALF中IL-10水平与CPIS评分无明显相关性。结论重症肺炎患者血液和支气管肺泡灌洗液中IL-6、IL-8的水平可以反映肺感染程度，IL-8、IL-10的水平及变化趋势可以反映患者预后情况。     

IL-4、IL-6、IL-10、TNF-α基因多态性与药物性肝损伤相关性的Meta分析

目的：探讨IL-4、IL-6、IL-10和TNF-α基因多态性与药物性肝损伤（drug-induced liver injury，DILI） 易感性关系。方法：检索Pubmed、Web of Science、Cochrane Library、EMBASE、知网与万方数据库，查找建库有关IL-4、IL-6、IL-10和TNF-α基因多态性与DILI发病风险的文献。应用STATA12.0对数据进行Meta分析。结果：共纳入10篇文献，共包括717例DILI患者和1 674例正常对照。所有研究都纳入Meta分析发现IL-6 rs1800796G>C中G等位基因携带者（OR=2.507，95% CI[1.542，4.074]，P=0.000）患DILI的风险显著升高，而TNF-α rs1800629G>A中G等位基因携带者（OR=0.715，95% CI[0.524，0.976]，P=0.035）患DILI的风险显著降低。在剔除一项显著的异质性研究后，携带IL-6 rs2066992G>T中G等位基因人群（OR=2.465，95% CI[1.506，4.036]，P=0.000）人群患DILI风险显著增加，而携带IL-10 rs1800872A>C中C等位基因（OR=0.818，95% CI[0.679，0.985]，P=0.034）人群患DILI风险则显著降低。本研究暂未发现IL-4各基因位点基因型与DILI有明显关联性。结论：TNF-α（rs1800629G>A）、IL-6（rs1800796G>C、rs2066992G>T）与IL-10（rs1800872A>C）与DILI发生有一定的关联性。     

炎性细胞因子在大鼠缺氧缺血性脑损伤中含量变化及其意义

目的:检测SD大鼠脑缺氧缺血后脑组织中IL-1、IL-6和IL-8 mRNA的表达,探讨IL-1、IL-6和IL-8在大鼠缺氧缺血性脑损伤(HIBD)中变化规律及其作用。方法:通过结扎左颈总动脉致大鼠脑急性缺血,后给8%氧气 92%氮气的混合气体致脑急性缺氧,建立大鼠脑急性缺血缺氧模型,在3个时相点采用rt-PCR方法测定假手术组、HIBD组脑组织中IL-1、IL-6和IL-8 mRNA含量变化。结果:HIBD组大脑皮质内IL-1和IL-8含量3d达到峰值,随后逐渐降低;大脑皮质内IL-6含量1d达到峰值,随后逐渐降低。缺血脑半球IL-1、IL-6和IL-8 mRNA含量较假手术组明显增高(P<0.05),且随着时间延长其表达量增加。结论:在大鼠急性缺氧缺血性脑损伤中,脑皮质内IL-1、IL-6和IL-8表达增强,IL-1、IL-6和IL-8参与了脑缺血缺氧后炎症反应的启动、发展过程。     

DNA疫苗用于防治艾滋病的研究概况

目的:将能表达抗原的DNA作为疫苗接种。方法:直接注射(皮下,肌肉等)含有DNA的制剂。结果:接种后机体可产生体液免疫和杀伤性T淋巴细胞(CTL)反应,并使机体产生抗病保护。结论:DNA疫苗将有可能用于防治人类艾滋病的理想化疫苗。     

IL-2、IL-6表达与ds-DNA在SLE检测中的相关性和临床意义

目的:探讨系统性红斑狼疮(SLE)患者血清中IL-2、IL-6的表达与ds-DNA的关系。方法:用酶联免疫吸附试验(ELISA)检测40例SLE患者血清中IL-2、IL-6和抗ds-DNA抗体水平。结果:SLE患者血清IL-2水平较正常组明显降低(P<0.01),而血清中IL-6水平较正常组增高(P<0.05)。结论:在SLE患者血清中IL-6水平与ds-DNA呈正相关,对于SLE的诊断和疗效观察有重要的临床意义。     

Modulation of immune response induced by co-administration of DNA vaccine encoding HBV surface antigen and HCV envelope antigen in BALB/c mice

Plasmid DNA vaccines encoding the hepatitis B virus (HBV) surface and hepatitis C virus (HCV) envelope antigens, respectively, were constructed, and attempt were made to find the possibility of a divalent vaccine against HBV and HCV. The expression of each plasmid in Cos-1 cells was confirmed using immunocytochemistry. To measure the induced immune response by these plasmids in vivo, female BALB/c mice were immunized intramuscularly with 100 microg of either both or just one of the plasmids. Anti-HBV and HCV-specific antibodies and related cytokines were evaluated to investigate the generation of both humoral and cellular immune responses. As a result, specific anti-HBV and anti-HCV serum antibodies from mice immunized with these plasmids were observed using immunoblot. The levels of IL-2 and RANTES showing a Th1 immune response were significantly increased, but there was no change in the level of IL-4 (Th2 immune response) in any of the immunized groups. Compared with each plasmid DNA vaccine, the combined vaccine elicited similar immune responses in both humoral and cell-mediated immunities. These results suggest that the combined DNA vaccine can induce not only comparable immunity experimentally without antigenic interference, but also humoral and Th1 dominant cellular immune responses. Therefore, they could serve as candidates for a simultaneous bivalent vaccine against HBV and HCV infections.     

替比夫定对慢性乙型肝炎患者血清中IL-6和IL-18的影响

目的 观察替比夫定(LdT)治疗前后慢性乙型肝炎(CHB)患者血清中白细胞介素 6(IL-6)和白细胞介素 18(IL-18)水平的变化,探讨替比夫定对CHB患者细胞免疫功能的影响.方法 设立健康对照组100例,CHB组96例,用ELISA方法检测各组中IL-6和IL-18的变化;CHB组加用替比夫定抗病毒治疗24周,观察治疗前后血清中IL-6、IL-18及病毒学指标的变化.结果 ①CHB患者血清中IL-6和IL-18水平较健康对照组明显升高,差异有统计学意义(P值均<0.01);②替比夫定抗病毒治疗后较治疗前血清中IL-6、IL-18及HBV DNA水平均下降,差异有统计学意义(P<0.05).结论 替比夫定通过抑制HBV复制,能够降低CHB患者血清中IL-6和IL-18的水平,可以改善CHB患者的细胞免疫功能.