系统性红斑狼疮相关新基因IFIT4的亚细胞定位及干扰素-α对其表达的影响

目的探讨系统性红斑狼疮(SLE)相关新基因IFIT4的组织细胞分布、亚细胞定位及干扰素(IFN)-α对其表达的影响。方法利用反转录聚合酶链反应(RT-PCR)检测IFIT4mRNA在各组织及免疫细胞中的表达;而后构建和转染绿色荧光蛋白(GFP)-IFIT4融合质粒入单核细胞,共聚焦显微镜观察IFIT4亚细胞定位;最后用Western-blot、qRT-PCR检测IFN-α和CpG-A刺激正常人外周血单个核细胞(PBMC)前后IFIT4、STAT1、RELB的表达差异。结果IFIT4mRNA主要表达在免疫相关组织和CD19 、CD8 、CD14 细胞;IFIT4蛋白定位于细胞质;其表达受IFN-!调控,CpG-A不直接参与IFIT4表达调控。结论IFIT4可能作为IFN-!效应分子在SLE免疫系统紊乱发病机制中发挥潜在致病作用。     

泛昔洛韦治疗慢性乙型肝炎的临床研究

目的评价泛昔洛韦片剂治疗经干扰素α治疗12周无应答的慢性乙型肝炎患者的疗效和安全性。方法212例患者接受3MU干扰素α治疗12周,复查乙型肝炎e抗原(HBeAg)、乙型肝炎病毒(HBV) DNA仍阳性、HBV DNA定量≥106拷贝/ml的患者,按随机双盲的方法,以1:1的比例分配到试验组和对照组治疗24周,停药后随访24周。结果治疗24周末,HBV DNA定量对数值比较,泛昔洛韦组由(6.54 ±1.26)拷贝/ml下降至(5.70±2.03)拷贝/ml,安慰剂组由(6.30±1.32)拷贝/ml上升至(6.51±1.65)拷贝/ml,x2=3.04,P<0.01;血清HBV DNA定量下降≥2log率比较,泛昔洛韦组为28.28% (28/99),安慰剂组为9.47%,x2=13.10,P<0.01;HBV DNA水平下降至<105拷贝/ml率比较,泛昔洛韦组为28.28%,安慰剂组为14.74%,P<0.05;泛昔洛韦组HBeAg阴转率为7.69%,安慰剂组为3.33%; 泛昔洛韦组HBeAg/抗-HBe血清转换率为4.40%,安慰剂组为2.22%,差异均无统计学意义;丙氨酸氨基转移酶复常率泛昔洛韦组为15.15%,安慰剂组为6.35%,P<0.05。HBV DNA定量<105拷贝/ml的患者停药24周反跳率泛昔洛韦组为25.00%,安慰剂组为14.29%,差异无统计学意义。结论泛昔洛韦治疗经干扰素α治疗12周无应答的慢性乙型肝炎患者能有效抑制其病毒复制,但HBeAg/抗-HBe的血清转换率变化不明显。试验6个月疗程内泛昔洛韦使用安全且耐受性良好。     

Prevention of interferon-alpha associated depression in psychiatric risk patients with chronic hepatitis C

BACKGROUND/AIMS: Interferon-alpha (IFN-alpha) induced depression is a major limitation for the treatment of chronic hepatitis C, especially for patients with psychiatric disorders. We prospectively studied the efficacy of a pre-emptive treatment with the antidepressant citalopram to prevent depression during hepatitis C treatment with pegylated IFN-alpha-2b plus ribavirin. METHODS: 14 HCV infected patients with psychiatric disorders received a prophylactic medication with citalopram (20mg/day) before and during therapy with IFN-alpha. The incidence of major depression was compared with 22 HCV infected patients with psychiatric disorders (group B; n=11) and without psychiatric risk factors (group C; n=11), who underwent IFN-alpha treatment without a pre-emptive antidepressant therapy. Depression was diagnosed by DSM-IV criteria. RESULTS: Pre-treatment of psychiatric patients with citalopram significantly reduced the incidence of major depression during the first 6 months of antiviral treatment as compared to the two control groups (group A 14% vs. 64% and 55% in group B and C; log-rank 6.89; df=2; P=0.032). Patients who developed symptoms of major depression during IFN therapy could also be improved by antidepressive treatment. CONCLUSIONS: Our open label pilot study, though small, clearly indicates that IFN alpha induced depression in psychiatric risk patients can be ameliorated by both the use of antidepressants as well as by intensive psychiatric care. However, larger, double blind placebo controlled trials in other patient populations are required to confirm these preliminary findings.     

Recombinant interferon-alpha,but not interferon-gamma is effective therapie for essential thrombocythemia

Summary Recombinant interferon-gamma with a starting dose of 0.5 mg 3×/week subcutaneously, was administered to 6 patients with essential thrombocythemia (median platelet count 1172×10⁹/1, range 602–1564). Four of the patients had received alkylating agents previously. Hematological remission, defined as a decrease in platelet counts to 350×10⁹/l, was observed in none of these patients. Subsequently 4 of these 6 patients, supplemented by 2 others were treated with interferonalpha_2c at a dose of 5×10⁶ U daily subcutaneously. Five patients showed hematological remission. In case of hematological remission the interferonalpha dosis was reduced to 5× an thereafter to 3× weekly 5×10⁶ U. During an observation period ranging from 12–41 weeks platelet counts remained normal in all patients. Side-effects were mild and consisted of fever, myalgias, malaise and itching occurring mainly during the first month of treatment. No dose adaptation was required. The patients treated previously with interferon-gamma experienced the side effects from this drug less tolerably than those from the alpha-compound. These observations suggest that recombinant interferonalpha may be an effective drug in treating essential thrombocythemia resulting in a sustained response.     

干扰素α对胃癌多药耐药细胞耐药性的影响

目的:研究干扰素α对SGC7901/VCR胃癌多药耐药细胞耐药性的影响。方法:用不同浓度的干扰素α(IFN-")(0、103、104、105U/mL)以不同时间(0、12、24、48、96h)长度作用于SGC7901/VCR胃癌多药耐药细胞,收集作用后的细胞,用RT-PCR方法检测多药耐药1(MDR1)基因mRNA随IFN-α作用的不同时间和浓度变化情况,用流式细胞仪检测MDR1蛋白表达随IFN-α作用的不同时间和浓度变化情况。用MTT方法检测经IFN-α(105U/mL)作用SGC7901/VCR细胞48h后,与不经过IFN-α作用的SGC7901/VCR细胞相比耐药谱的变化。结果:随作用时间增加和IFN-α浓度增大,MDR1的mRNA和蛋白的表达都减少,在α=0.05水平均有统计学意义;在IFN-α浓度为105U/mL,作用时间为48h,MDR1的mRNA和蛋白的表达都减少最明显。SGC7901/VCR细胞被IFN-α作用后,其对各化疗药物耐药性的变化为,对长春新碱和羟喜树碱的逆转倍数最大,IC50分别减少了22倍和12倍,最明显;其次为对5-氟尿嘧啶的耐药的变化;对丝裂霉素和卡铂的耐药性的逆转倍数不是很大。结论:IFN-α对SGC7901/VCR胃癌多药耐药细胞的耐药性有部分逆转的作用,但对不同抗癌机制的化疗药物逆转效果不同。其机制可能为抑制MDR1基因RNA的合成,进而影响MDR1蛋白的合成,最终减少MDR1蛋白对化疗药物的泵出效应。     

α-干扰素治疗HBeAg阳性慢性乙型肝炎血清IL-17水平的动态检测

目的:探讨IL-17在HBeAg阳性慢性乙型肝炎及其α-干扰素抗病毒过程中可能的作用及意义。方法:采用酶联免疫吸附法测定20例HBeAg阳性慢性乙型肝炎肝炎患者及11例健康对照者血清中的IL-17的水平,并对这20例患者干扰素治疗不同时间点的血清IL-17、肝功、HBeAg定量及HBVDNA定量进行检测。结果:HBeAg阳性慢性乙肝患者血清IL-17较健康人无明显升高;α-干扰素治疗后,应答组血清IL-17在18周后出现明显升高,而无应答组血清IL-17呈现水平波动;应答组中HBeAg转阴者较未转者血清IL-17水平在18周升高明显。结论:Th17细胞通过分泌IL-17可能参与HBeAg阳性慢性乙肝患者α-干扰素治疗后期的持久抗病毒作用。     

干扰素α治疗HBeAg阳性慢性乙型肝炎儿童疗效的荟萃分析

目的 评价IFN-α治疗HBeAg阳性慢性乙型肝炎(CHB)儿童的疗效及安全性.方法 检索美国国立医学图书馆数据库(PubMed)和中国期刊全文数据库(CHKD)从建库至2006年4月所收录的比较IFN-α与非抗病毒药物(安慰剂或空白对照)治疗HBeAg阳性CHB儿童的随机对照试验论文.由两名评价员独立筛查文献,评价质量和提取资料.采用Jadad量表及随机分配方案隐藏方法评估纳入试验的方法学质量.采用X2检验鉴定研究间异质性,使用随机效应或固定效应模型合并研究.采用敏感度分析方法探讨试验结果的影响因素.结果 共纳入7个随机对照试验,HBsAg和HBeAg阳性的CHB患儿360例.荟萃(Meta)分析结果显示,治疗结束时,IFN-α组HBeAg转阴率高于对照组[22.1%比6.7%,OR 3.56,95%CI(1.74,7.28),P=0.0005],HBV DNA转阴率高于对照组[33.7%比12.6%,OR 3.50,95%CI(2.03,6.06),P＜0.01],HBsAg转阴率高于对照组[6.5%比0.5%,OR 7.10,95%CI(1.52,33.12),P=0.01],HBeAg血清转换率高于对照组[17.3%比2.9%,OR 5.62,95%CI(1.65,19.18),P=0.006],两组差异均有统计学意义,但HBsAg血清转换与对照组相比[2.0%比0,OR 3.55,95%CI(0.35,35.93),P=0.28],ALT复常率与对照组相比[24.2%比16.2%,OR 1.72,95%CI(0.84,3.52),P=0.14],两组差异无统计学意义.结论 HBeAg阳性的CHB患儿经IFN-α治疗可达到HBeAg转阴、HBV DNA转阴、HBsAg转阴及HBeAg血清学转换的效应,但未能实现HBsAg血清学转换及ALT复常.受原研究质量和不同研究干预措施差异的影响,IFN-α的治疗效应还需要严格设计的、大样本的随机双盲对照试验来进一步验证和支持.     

干扰素和黄芪对心肌炎小鼠心肌细胞凋亡的影响

方法：BALB/c小鼠腹腔接种半数组织感染量（TCID50）为108/ml的柯萨奇B3病毒0.1?ml。干扰素治疗组于接种病毒后24?h起腹腔注射α1b 干扰素104IU/g体重，1次/d，连用5?d。黄芪治疗组于接种病毒后24?h起灌喂黄芪颗粒30?mg/g体重，1次/d，共5?d。接种病毒后第7、14、21天分别处死小鼠，原位TUNEL法检测心肌细胞凋亡，ELISA法测定血清肿瘤坏死因子 α含量。结果：病毒性心肌炎小鼠心肌细胞凋亡百分率明显增高，血清肿瘤坏死因子 α含量增加，干扰素和黄芪治疗可降低心肌细胞凋亡百分率及血清肿瘤坏死因子 α含量。结论：α 干扰素和黄芪有抑制心肌细胞凋亡作用。     

A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses

Interferon-alpha (IFN-) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN- in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m² per day) or high (5 MU/m² per day) target dose of IFN-. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN- actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) (p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN- because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN- are as effective as high doses in the treatment of CML.The authors listed about wrote this contribution on behalf of the Spanish Group on IFN and CML     

Interferon Production in Children with Respiratory Diseases

ABSTRACT. In 110 children aged between 6 months and 18 years the ability of leukocytes to produce the leukocyte interferon (IFN-alpha) in vitro was studied. The decrease or disappearance of IFN-alpha production was observed in some children with chronic or repeated respiratory diseases and in the majority of children who had been treated with prednisone. Increased production of IFN-alpha was found in a child with hypogammaglobulinemia and bronchopneumonia. In children affected by allergic or autoimmune diseases or bacterial infections IFN-alpha production was mostly normal. Age and sex had no influence on the production of IFN-alpha.