慢性丙型肝炎患者α干扰素和α干扰素受体1的检测

目的建立检测外周血单个核细胞α干扰素受体1(IFNAR1)及检测诱导表达α干扰素(IFN-α)的方法,评价慢性丙型肝炎患者外周血单个核细胞(PBMC)细胞免疫功能与α干扰素治疗的关系。方法Poly IC体外刺激正常对照组和慢性丙型肝炎病毒(HCV)感染组患者PBMC,利用病毒保护试验研究干扰素治疗前后患者PBMC表达的干扰素抗病毒生物学活性差异;IFN-α治疗前后,RT-PCR检测慢性丙型肝炎患者不同干扰素应答组患者PBMC IFNAR1表达的变化。结果对照组PBMC分泌的干扰素活性显著高于慢性丙型肝炎患者应答组患者(P<0.001);干扰素应答组患者PBMC分泌的干扰素活性随治疗时间延长而增加,治疗1个月后显著高于无应答组患者PBMC分泌的干扰素活性(P<0.01),后者始终处于低下水平;IFN-α治疗期间干扰素应答组患者PBMC IFNAR1水平从治疗前的高表达而逐渐减少,正常对照和干扰素无应答组患者PBMC IFNAR1的表达始终较低。结论慢性HCV感染患者的细胞免疫功能受损,不能正常表达IFN-α,但应答组患者经干扰素治疗后IFN-α表达能力逐渐恢复;干扰素无应答组患者PBMC IFNAR1表达受到严重抑制;慢性丙型肝炎患者PBMCIFN-α活性检测及IFNAR1检测结果也许可以作为干扰素治疗预后的判断指标。     

血清IL-18与IL-10在慢性丙型肝炎发病中作用的临床研究

目的探讨白细胞介素(IL)-18与IL-10在慢性丙型肝炎发病中的作用,并观察干扰素抗病毒治疗对其水平的影响。方法采用酶联免疫吸附试验(ELISA)检测10例正常对照者、24例丙型肝炎病毒(HCV)携带者、27例慢性丙型肝炎患者(干扰素治疗前、后)血清中IL-18与IL-10水平。结果慢性丙型肝炎患者血清中IL-18与IL-10显著高于正常对照者(P<0.05)及HCV携带者(P<0.05),且其值与血清丙氨酸转氨酶值呈显著正相关;经干扰素治疗后,IL-18与IL-10水平均明显降低(P<0.05);干扰素治疗前,血清中IL-10水平由高到低依次为:治疗无应答组>部分应答组>完全应答组。结论IL-18与IL-10共同参与慢性丙型肝炎的发病,并可用于评价干扰素对机体免疫状态的影响;血清中IL-10水平对预测抗病毒疗效有重要意义。     

慢性丙型肝炎患者血浆IL-12p40水平测定及意义

目的:探讨慢性丙型肝炎患者血浆IL-12 p40水平变化及其与病毒载量、干扰素疗效的关系。方法:采用双抗体夹心ELISA法测定62例慢性丙型肝炎患者干扰素治疗前后及32例健康体检者血浆IL-12p40水平,采用速率法和FQ-PCR法分别测定丙型肝炎患者血浆ALT活性和HCV RNA水平。结果:丙型肝炎组血浆IL-12p40水平(pg/ml)低于对照组(P<0.01)。丙型肝炎患者血浆IL-12p40水平与ALT活性(U/I)呈负相关(r=-0.420,P<0.01)。丙型肝炎患者中高水平HCV RNA组血浆IL-12p40水平低于低水平HCV RNA组(P<0.05)。治疗前干扰素应答组与无应答组血浆IL-12p40水平差别无统计学意义,治疗后应答组IL-12p40水平明显增加(P<0.05)。结论:慢性丙型肝炎患者存在IL-12p40水平低下,其水平变化可反应患者体内HCV病毒载量及肝损程度,并与干扰素应答有一定关联,但在治疗前尚不能预测疗效。     

慢性乙型肝炎患者外周单个核细胞分泌细胞因子的实验研究

目的探讨慢性乙肝患者外周血单个核细胞(PBMC)分泌肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)、白细胞介素6(IL-6)水平及与病毒载量的关系。方法采用ELISA法测定60例正常人和138例不同病程慢性乙肝患者PBMC中经植物血凝素(PHA)刺激前后TNF-α、IFNγ-、IL-6在上清液中的表达水平,并用荧光定量PCR法检测PBMC中HBV DNA水平。结果正常对照组及各种慢性乙肝患者PBMC上清液中TNF-α、IFNγ-、IL-6均有表达,HBV感染者三种细胞因子表达水平高于对照组,随着病情程度加重,表达水平逐渐增高(P<0.05);经PHA刺激后对照组及患者组TNFα-、IFN-γ、IL-6水平均有明显增高(P<0.01),但患者组升高水平均低于对照组(P<0.05);随着HBV DNA水平增高,PBMC中TNF-α、IFN-γ表达水平逐渐减低,而IL-6活性逐渐增高(P<0.05)。结论慢性乙肝患者PBMC可分泌TNF-α、IFNγ-、IL-6,其表达水平与宿主病毒载量有关。Th1/Th2细胞因子失衡在PBMC抗病毒免疫受抑,乙型肝炎慢性化进程中起着重要作用。     

α干扰素对慢性乙型肝炎患者血清肝纤维化指标的影响

[目的]研究α干扰素(IFN-α)对慢性乙型肝炎患者血清肝纤维化指标的影响.[方法]32例慢性乙型肝炎患者,以肌肉注射IFN-α1b 3MU,隔日1次,用酶联免疫吸附法(ELISA法)检测血清中透明质酸(HA)、层粘蛋白(LN)、Ⅳ型肢原(C-Ⅳ)及转化生长因子-β1(TGF-β1)含量,观察治疗前后上述血清指标的变化情况.[结果]经IFN-α治疗6个月后,血清HA、LN、C-Ⅳ、TGF-β1含量均较治疗前明显下降,差异有统计学意义(P<0.01);将32例慢性乙型肝炎患者分为3组:完全应答组19例、部分应答组8例,无应答组5例.只有完全应答组患者在治疗后血清LN、HA、C-Ⅳ、TGF-β1含量达到正常水平,并且上述指标的下降程度在完全应答组最明显(F≥103.6,P<0.01),部分应答组和无应答组织间比较差异无统计学意义.[结论]α干扰素(IFN-α)可以改善慢性乙型肝炎患者的肝纤维化.     

干扰素α联合核苷类药物治疗慢性乙型肝炎的疗效观察

目的:观察干扰素α联合核苷类药物治疗慢性乙型肝炎的疗效.方法:59例慢性乙型肝炎患者接受了干扰素α联合拉米夫定治疗(治疗组),55例同病患者仅接受拉米夫定(对照组),治疗前后测试肝功能和病毒复制指标.结果:治疗组中有50例(84.76%)发生了治疗应答,其中完全应答27例,部分应答14例,无应答9例.对照组中有39例(69.09%)发生了治疗应答,其中完全应答11例,部分应答18例,无应答10例(χ2=6.037,P＜0.02).两组患者治疗前血清ALT和AST、HBV-DNA和HbeAg浓度无明显区别(P均＜0.05),治疗后ALT和AST、HBV-DNA和HbeAg浓度均较治疗前明显下降,同时治疗组治疗后上述各检测值均明显优于对照组同期结果(P均＜0.05～0.01).结论:干扰素α联合核苷类药物治疗慢性乙型肝炎疗效更佳.     

α2b干扰素治疗慢性丙肝患者的临床研究

目的：探讨α2b干扰素对慢性丙肝患外周血单个核细胞（PBMC）内HCV的治疗效果。方法：采用国产α2b干扰素（300MU／d）治疗，3个月为一疗程，共2个疗程，并设常规治疗组（VitC、门冬氨酸）为对照。于疗程结束后分别检测患PBMC内HCV－RNA和血清内HCV－RNA、抗－HCV。结果：α2b干扰素治疗组2个疗程后慢性丙肝患PBMC、血清内HCV－RNA和抗－HCV转阴率分别为42．31％（11／26）、57．69％（15／26）、65．38％（17／26），常规治疗组慢性丙肝患PBMC、血清内HCV－RNA和抗－HCV转阴率分别为13．64％（3／22）、22．73％（5／22）、27．27％（6／22），两组相比，差异有显性（P＜0．05）。结论：α2b干扰对PBMC内HCV－RNA具有肯定的治疗作用，其疗效优于常规治疗组。     

IFN-α2b对慢性乙型肝炎患者外周血单个核细胞内HBV-DNA阴转和对CD25的诱导作用

目的探讨IFN-α2b对慢性乙型肝炎患者HBV-DNA的治疗效果及对CD25的诱导作用. 方法将患者分为A(66例)、B(44例)两组,分别采用IFN-α2b和常规治疗,PCR法动态检测患者外周血单个核细胞(PBMC)内和血清中HBV-DNA,生物素-链霉亲和素(BSA)法检测CD25表达水平,实时(real-time) PCR法检测CD25 mRNA含量,动态检测抗-IFN-IgG水平. 结果 IFN-α2b治疗24、48周后,患者PBMC内、血清中HBV-DNA和HBeAg阴转率分别为36.36%、39.39%、40.91%和42.42%、51.52%、53.03%,与常规组相比差异有显著性(P<0.05～P<0.01);干扰素治疗后,ALT、AST、ALT/AST水平分别为(33.4±12.6)U/ml、(34.3±10.7)U/ml、(0.9±0.2)U/ml,与常规组相比差异有显著性(P<0.01);慢性乙型肝炎患者静息态和诱导态CD25水平均降低,干扰素治疗后,静息态和诱导态CD25水平显著升高,其CD25 mRNA含量亦同步升高,与常规组相比差异有显著性(P<0.01);IFN-α2b治疗48周抗-IFN-IgG阳性率仅6.06%,与常规组相比差异无显著性(P>0.05). 结论 IFN-α2b对PBMC、血清HBV-DNA和HBeAg均有较好阴转效果,阴转率明显高于常规疗法;IFN-α2b可诱导慢性乙型肝炎患者表达CD25,促进T细胞活化发挥抗病毒作用;IFN-α2b自身免疫原性较弱,治疗过程中诱导机体产生低水平的抗-IFN-IgG,对IFN-α2b的抑制作用较弱.     

老年慢性乙肝患者炎症因子水平与α-干扰素抗病毒应答的相关性研究

目的对老年慢性乙肝患者炎症因子水平与α-干扰素抗病毒应答的相关性进行研究,为临床治疗提供参考。方法对荆州市中心医院2010年10月-2015年10期间诊治的100例老年慢性乙肝患者在α-干扰素抗病毒治疗前、治疗12、24周后抽血测定血清炎症因子,包括γ干扰素((interferon-γ,IFN-γ)、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、转化生长因子β(transforming growth factorβ,TGF-β)、炎性小体3(pyrin containing 3 gene,NLPR3)、核因子κB(nuclear factorκB,NF-κB)、单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)、白细胞介素1α(interleukin 1α,IL1α)、白细胞介素1β(interleukin 1β,IL1β)、白细胞介素2(interleukin 2,IL2)和白细胞介素6(interleukin 6,IL6)和CRP(C-reaction protein)。治疗12周后,根据ALT、HBV DNA判定应答情况,分析有应答组患者和无应答组患者血清炎症因子水平变化。结果α-干扰素抗病毒治疗12周后,100例乙肝患者中完全应答30人,部分应答34人,无应答组36人:免疫应答组(n=64,包括完全应答、部分应答者)及无应答组(n=36)治疗前炎症因子水平差异均无统计学意义(P0.05);有应答组患者经α-干扰素抗病毒治疗12周和24周后患者血清中IFN-γ、TNF-α水平显著升高,而CRP、IL1α、IL1β、IL2、IL6、TGF-β、NLPR3、NF-κB、MCP-1水平显著降低,且随着治疗时间的延长上述因子变化更显著(P0.05)。结论老年慢性乙肝患者白细胞介素等炎症因子水平与α-干扰素抗病毒应答有密切关系。     

重组人干扰素α-2b凝胶联合阿达帕林凝胶治疗扁平疣60例的疗效观察

目的 探讨重组人干扰素α-2b凝胶和阿达帕林凝胶联合治疗扁平疣的临床疗效.方法 采取重组人干扰素α-2b凝胶(观察组)或联合阿达帕林凝胶(对照组)外用治疗扁平疣患者各30例,选择健康体检者20例作为正常组,检测治疗前后扁平疣患者血清白介素-2(interleukin-2,IL-2)及干扰素-γ(interferon-γ,IFN-γ)水平变化.结果 观察组有效率为96.7％,对照组有效率为73.3％,差异有统计学意义(P＜0.05).治疗前患者血清IL-2水平及IFN-γ水平均显著低于正常组(P＜0.05);治疗后观察组的IL-2水平及IFN-γ水平升高(P＜0.05),而对照组治疗前后IL-2、IFN-γ水平差异无显著性.结论 重组人干扰素αt-2b凝胶联合阿达帕林凝胶治疗扁平疣,疗效显著.     

干扰素诱导抗病毒蛋白基因多态性与肝炎疗效的相关性

IFN治疗是慢性病毒性肝炎病因治疗的主要手段,但是相同的治疗方法在不同的患者中,疗效差异很大,可能与不同个体的免疫遗传差异有关,即不同个体IFN诱导的抗病毒蛋白的基因多态性不同,进而影响了慢性肝炎疗效。现就IFN诱导抗病毒蛋白的基因多态性与慢性肝炎抗病毒疗效的相关性进行综述。     

丙型肝炎病毒与干扰素抵抗

干扰素(IFN)在人体防御病毒感染以及治疗病毒性疾病的过程中起着非常重要的作用,它是目前治疗HCV感染的唯一方法。但是,像许多病毒一样,HCV也有对IFN产生抵抗的现象。研究表明,HCV持续存在及IFN治疗是否有效可能与HCV表达的一些蛋白质抑制IFN抗病毒活性、HCV的基因型、HCV变异以及宿主因素等有关。     

Silicate minerals and the interferon system

Natural-occurring minerals representative of six silicate classes were examined for their influence on interferon induction by influenza virus in Rhesus monkey kidney (LLC-MK2) cell monolayers. Minerals within the classes nesosilicate, sorosilicate, cyclosilicate, and inosilicate exhibited either little or marked (50% or greater) inhibition of interferon induction. Within the inosilicate class, however, minerals of the pyroxenoid group (wollastonite, pectolite, and rhodonite) all significantly showed a two- to threefold increase in interferon production. Silicate materials in the phyllosilicate and tectosilicate classes all showed inhibitory activity for the induction process. When silicate minerals were coated with the polymer poly(4-vinylpyridine-N-oxide), the inhibitory activity of silicates on viral interferon induction was counteracted. Of nine randomly selected silicate minerals, which inhibited viral interferon induction, none adversely affected the ability of exogenous interferon to confer antiviral cellular resistance. Increased levels of influenza virus multiplication concomitant with decreased levels of interferon occurred in cell monolayers pretreated with silicates. The findings of this study demonstrate the diverse effects of minerals representative of different silicate classes on the interferon system and indicate that certain silicates in compromising the viral interferon induction process may increase susceptibility to viral infection.     

干扰素在早期胚胎发育中的作用

干扰素是在免疫应答中起着重要作用的一类细胞因子,具有强效的抗病毒、抗肿瘤活性以及免疫调节作用。干扰素在早期胚胎发育、维持妊娠中也具有重要作用,该文结合实验室的研究工作对这一领域的研究进展进行综述。     

干扰素及其抗病毒作用研究概况

IFN作为一组具有多功能免疫活性的蛋白质,具有抗病毒、抗肿瘤和免疫调节等功能,已经成为当今免疫学、肿瘤学、病毒学和分子生物学研究最为活跃的研究热点之一.此文就IFN及其抗病毒作用的研究作了综述.     

干扰素及其抗病毒作用研究概况

IFN作为一组具有多功能免疫活性的蛋白质,具有抗病毒、抗肿瘤和免疫调节等功能,已经成为当今免疫学、肿瘤学、病毒学和分子生物学研究最为活跃的研究热点之一.此文就IFN及其抗病毒作用的研究作了综述.     

Weight change and peptide hormone responses in patients receiving interferon

The purpose of this pilot study was to describe body weight status and peptide hormone responses in patients receiving interferon (IFN) therapy for renal cell carcinoma. Eighteen patients were on therapy for approximately two to three months. Mean weight loss of the patients was 2.2 ± 0.9 kg (mean ± SEM) or 4.9± 0.9% of prestudy weight. Of the 18 patients, 6 were further evaluated for peptide hormone responses to meal stimulation before and after treatment (mean: 1.5 months). These subjects had a mean weight loss of 4.3 ± 1.6 kg or 7.0 ±3.5% of prestudy weight. Blood was drawn from subjects before and six times after they had consumed a defined formula liquid meal to provoke enteroinsular peptide release. It was discovered that one‐half of this group (n = 3; Group A) had some glucose intolerance following IFN therapy, despite increased response of insulin, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (PP) to meal stimulation. Further, patients in Group A had a weight loss of — 11.7 ± 2.7% of prestudy weight, whereas the other three patients (Group B) experienced a mean loss of ‐ 2.3 ± 1.2% (p < 0.04). The three subjects characterized by the smaller loss of prestudy weight (Group B) had decreased glucose response to meal stimulation, despite decreased responses of insulin and GIP. Response of PP was slightly increased with treatment in group B, but the increase was not as large as that in Group A. These data may suggest that extreme weigh t loss and altered peptide hormone response occur in a subset of cancer patients receiving interferon therapy.     

Weight change and peptide hormone responses in patients receiving interferon

The purpose of this pilot study was to describe body weight status and peptide hormone responses in patients receiving interferon (IFN) therapy for renal cell carcinoma. Eighteen patients were on therapy for approximately two to three months. Mean weight loss of the patients was 2.2 +/- 0.9 kg (mean +/- SEM) or 4.9 +/- 0.9% of prestudy weight. Of the 18 patients, 6 were further evaluated for peptide hormone responses to meal stimulation before and after treatment (mean: 1.5 months). These subjects had a mean weight loss of 4.3 +/- 1.6 kg or 7.0 +/- 3.5% of prestudy weight. Blood was drawn from subjects before and six times after they had consumed a defined formula liquid meal to provoke enteroinsular peptide release. It was discovered that one-half of this group (n = 3; Group A) had some glucose intolerance following IFN therapy, despite increased response of insulin, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (PP) to meal stimulation. Further, patients in Group A had a weight loss of -11.7 +/- 2.7% of prestudy weight, whereas the other three patients (Group B) experienced a mean loss of -2.3 +/- 1.2% (p less than 0.04). The three subjects characterized by the smaller loss of prestudy weight (Group B) had decreased glucose response to meal stimulation, despite decreased responses of insulin and GIP. Response of PP was slightly increased with treatment in group B, but the increase was not as large as that in Group A. These data may suggest that extreme weight loss and altered peptide hormone response occur in a subset of cancer patients receiving interferon therapy.