病毒性肝炎患者IL－1、IL－6和TNFα活性的检测

检测了甲、乙型病毒性肝炎患者外周血单个核细胞（ＰＢＭＣｓ）ＩＬ－１、ＩＬ－６和ＴＮＦα的诱生活性及其血清中活性。结果表明，乙型慢性活动性肝炎（ＣＡＨ）、乙型肝炎后肝硬化（ＨＣ）和乙型重型肝炎（ＳＨ）ＰＢＭＣｓ经脂多糖诱导后，ＩＬ－１活性分别为３５３１．１±８８２．７Ｕ／ｍ１、２７６９．７±７３０．４±Ｕ／ｍｌ和５３２９．３±１０８９．３Ｕ／ｍｌ，高于正常对照组（Ｐ＜０．０５或（０．０１）；ＩＬ－６诱生活性分别为３８．９０±１４．７５Ｕ／ｍ１、２．４５±１８．８５Ｕ／ｍｌ和７１．９５±２８．０５Ｕ／ｍｌ（与正常对照组相比，ｐ＜０．０５或＜０．０１）；ＴＮＦα诱生活性在乙型慢性迁延性肝炎（ＣＰＨ）、ＣＡＨ、ＨＣ和ＳＨ中分别为３３．２３±７．２５Ｕ／ｍｌ、６．９９±１．８４Ｕ／ｍ１、４．２９±２．１７Ｕ／ｍｌ和８６．７０±２４．１８Ｕ／ｍｌ，与对照组相比Ｐ＜０．０５或Ｐ＜０．０１。各型患者血清中ＩＬ－１、ＩＬ－６和ＴＮＦα活性均有不同程度的增高。文中对ＳＨ患者ＩＬ－１、ＩＬ－６和ＴＮＦα之间的相互关系进行了探讨。     

促炎症细胞因子、T细胞亚群在小儿过敏性紫癜不同病期的变化

目的：探讨促炎症细胞因子（ＩＬ－６１、ＩＬ－８、ＴＮＦ－α）以及Ｔ细胞亚群在小儿过敏性紫癜发病中的作用。方法：采用双抗体夹心ＥＬＩＳＡ法检测３０例急性期２１例恢复期及２８例健康儿童血清及外周血单个核细胞（ＰＢＭＣ）培养上清液ＩＬ－６、ＩＬ－８及ＴＮＦ－α水平,以及外周血Ｔ细胞及其亚群的变化。结果：急性期血清及ＰＢＭＣ上清液ＩＬ－６、ＩＬ－８、ＴＮＦ－α水平明显高于恢复期和对照,且以ＩＬ－８、ＴＮＦ     

Graves病患者治疗前后血清TNF-α和IL-6的动态变化

目的：检测Ｇｒａｖｅｓ病（ＣＤ）患者治疗前后血清白细胞介素－６（ＩＬ－６）和肿瘤坏死因子（ＴＮＦ－α）的动态变化，探讨甸子与ＣＤ发生发展之间的内在联系。方法：于治疗前和治疗后８周与２４周采集患者静脉血，分别采用放免法和超敏酶免法检测血清ＩＬ－６和ＴＮＦ－α含量。结果：ＣＤ患者血清ＩＬ－６和ＴＮＦ－α水平明显升高；应用抗 状腺药物８周和２４周甲状腺激素恢复正常后，ＩＬ－６和ＴＮＦ－α水平明显升高；应     

IL—10在慢性肝病中的抗纤维化效应

ＩＬ－１０是目前发现的一种重要抗炎症作用细胞因子之一。最近研究ＩＬ－１０与慢性肝病变发生发展关系密切。本文着重综述近来国内外关于ＩＬ－１０在抑制炎症细胞、ＨＳＣ,减少细胞因子ＴＮＦα、ＩＬ－６等产生,影响核因子ＮＦ－ｋＢ活性,调节肝再生反应和对ＥＣＭ胶原酶表达改变等方面均可能参与抗肝纤维化效应的研究进展。     

亚急性重型肝炎患者TNF-α和IL-1表达及IL-4对其的调控

目的：分析ＩＬ－４对亚急性重型肝炎（亚重肝）患者外周血单个核细胞（ＰＢＭＣＳ）ＴＮＦ－α和ＩＬ－１的调控作用,评价ＩＬ－４在亚重肝治疗中的潜在价值。方法：应用细胞生物学、免疫组化和ＲＴ－ＰＣＲ等方面测定ＰＢＭＣＳ ＴＮＦ－α、ＩＬ－１的表达。结果：亚重肝患者ＰＢＭＣＳ ＴＮＦ－α、ＩＬ－１表达水平均较正常人显著增高血糖素含量和虽然ＩＬ－４ ＭＲＮＡ及蛋白质的表达与正常人比较一差异无但ＩＬ－４ ＭＲ     

过敏性紫癜患儿血清TNF-α,IL-6和IL-8变化的意义

ＴＮＦα,ＩＬ６和ＩＬ８是具有多种生物学活性的细胞因子,也是重要的炎症因子,可参与许多变态反应性疾病和自身免疫性疾病的发病机制。我们对６８例过敏性紫癜(ＨＳＰ)患儿血清ＴＮＦα,ＩＬ６和ＩＬ８水平的变化及相关性进行了研究,旨在探讨它们在ＨＳＰ的毛细血管炎和过敏性紫癜性肾炎(ＨＳＰＮ)形成中的作用。１材料和方法１．１材料按１９９０年,美国风湿病协会制定的诊断标准〔１〕,选择１９９７-０６～１９９９-０１,我院确诊为ＨＳＰ的住院患儿共６８例,男３９例,女２９例,年龄５～１４岁。其中单纯型１３例,关节型和／或腹型１７例…     

分泌抗rHuIL－6McAb杂交瘤细胞系的建立及其应用研究

应用常规方法建立了４株稳定分泌抗重组人ＩＬ－６（ｒＨｕＩＬ－６）单克隆抗体（ＭｃＡｂ）的小鼠杂交瘤细胞系１Ｈ３、２Ａ１０、３Ａ３和４Ｂ１。其中，１Ｈ３为ＩｇＧ２ｂ（ｋ），２Ａ１０为ＩｇＧ１（ｋ），３Ａ３和４Ｂ１为ＩｇＧ２ａ（ｋ）。４株ＭｃＡｂ特异性强，与细胞因子ＩＬ－１β、ＩＬ－３、ＩＬ－８、ＴＮＦ－α、ＧＭ－ＳＣＦ、ＩＣＡＭ－１，以及受体菌菌体蛋白成分均无交叉反应。间接ＥＬＩＳＡ测定小鼠腹水ＭｃＡｂ效价为１０（－６）～１０（－８）。应用识别不同表位的ＭｃＡｂ建立了双抗体夹心ＥＬＩＳＡ法检测ＩＬ－６，敏感性为１００ｐｇ／ｍｌ。初步应用表明可用于临床标本的检测。     

乙型肝炎、肝硬化患者外周血中IL—1β和IL—4水平的变化

ＩＬ－１是一种单核因子,主要由活化的单核—巨噬细胞产生,ＩＬ－１可作用于机体的各个系统,如参与免疫调节,介导炎症反应和影响组织代谢。ＩＬ－４是一种由ＴＨ２细胞产生的具有多种生物学活性的细胞因子,ＩＬ－４可抑制单核—巨噬细胞分泌ＩＬ－１和ＴＮＦ－α,而且促进ＩＬ－１受体拮抗剂的表达。我们对慢性乙肝、肝硬化患者血清中ＩＬ－１β、ＩＬ－４水平进行了检测,旨在探讨ＩＬ－１β和ＩＬ－４在肝炎发病过程中的作用。１材料与方法１．１病例选择慢性乙型肝炎患者２５例（男２１例,女６例,年龄２２－６０岁）,肝硬化患者…     

TNF_(-α)、IL-6和IL-8在消化道肿瘤患者围手术期的表达

肿瘤坏死因子（ＴＮＦ α）、白细胞介素 ６（ＩＬ ６）和白细胞介素 ８（ＩＬ ８）具有广泛的生物学活性。为探讨肿瘤病人的细胞免疫功能,我们对４７例消化道恶性肿瘤患者手术前后血清ＴＮＦ α、ＩＬ ６和ＩＬ ８水平进行了检测,报告如下。１材料和方法１１...     

α-黑素细胞刺激素体外对星形胶质细胞产生NO和前炎性细胞因子的影响

目的：研究α－黑素细胞刺激素（α－ＭＳＨ）对ＬＰＳ诱导星形胶质细胞产生ＮＯ和前炎性细胞因子的影响。探讨α－ＭＳＨ的抗炎作用机制。方法：分别用ＬＰＳ或α－ＭＳＨ＋ＬＰＳ处理体外培养的大鼠脑星形胶质细胞,用Ｇｒｉｅｓｓ试剂测定ＮＯ,以ＭＴＴ显色法检测ＩＬ－１、ＩＬ－６和ＴＮＦ－α,采用半定量ＲＴ－ＰＣＲ检测ＭＩＦｍＲＮＡ表达。结果：体外培养的星形胶质细胞在ＬＰＳ刺激下产生ＮＯ、ＩＬ－１、ＩＬ－６、ＴＮＦ－α和表达ＭＩＦｍＲＮＡ表达。结果：体外的星形胶质细胞在ＬＰＳ刺激下产生ＮＯ、ＩＬ－１、ＩＬ－６、ＴＮＦ－α和表达ＭＩＦｍＲＮＡ显著增高;若同时给予ＬＰＳ和α－ＭＳＨ,可明显降低ＮＯ、ＩＬ－１、ＩＬ－６和ＴＮＦ－α的产生以及ＭＩＦｍＲＮＡ表达。结论：Ｒ昧α－ＭＳＨ抑制星形胶质细胞产生ＮＯ和前炎性细胞因子与其抑制中枢神     

IL-21的生物学功能及其在病毒感染中的作用

IL-21是最近发现的一种Ⅰ型细胞因子,由活化的CD4^＋T细胞产生,特别是Th2细胞。IL-21R存正常的淋巴组织包括脾、胸腺、淋巴结、外周血淋巴细胞、纤维化肺组织中都有表达。IL-21特异性结合IL-21R介导多种生物学效应,对不同阶段B、T淋巴细胞的分化和自然杀伤（NK）细胞的增殖均起重要作用。因此IL-21有着广泛的生物学功能,在各种疾病包括病毒感染中扮演着重要的角色。     

CTLA4-Ig在小鼠病毒性心肌炎中作用机制的研究

目的 探讨细胞毒T淋巴细胞相关抗原4融合蛋白(CTLA4-Ig)对柯萨舒B3(CVB3)病毒性心肌炎(VMC)小鼠死亡率、心肌病理改变与病毒滴度、CTLA4蛋白表达及Th1/Th2平衡的影响.方法 将106只BALB/c小鼠随机分为CTLA4-Ig组16只、病毒组40只、IgG组40只及正常对照组10只,于接种病毒后第7天处死所有小鼠,采用光镜检查心肌病理变化和实时荧光定量PCR(RQ-PCR)检测心肌组织中CVB3 mRNA的表达,免疫组化法检测CTLA4蛋白的表达,取外周血应用酶联免疫吸附法(ELISA)检测血清IL-2、IL-4及IFN-γ的含最.结果 CTLA4-Ig组小鼠死亡率、心肌病理积分、心肌CVB3 mRNA均低于病毒对照组(P均<0.05);CTLA4-Ig组小鼠心肌组织中CTLA4表达较病毒组明显增加(P<0.05);病毒组小鼠血清IFN-γ水平明显高于正常对照组小鼠(P<0.01),IL-4水平明显低于正常对照组小鼠(P<0.01),两组小鼠间IL-2的水平差异无统计学意义(P>0.05).CTLA4-Ig组小鼠血清IL-4水平明显高于病毒组及IgG组(P均<0.01),IFN-γ水平低于病毒组及IgG组(P均<0.01),三组小鼠血清IL-2水平的差异无统计学意义(P均>0.05).结论 CTLA4-Ig可减轻VMC小鼠心肌炎症,降低心肌病毒滴度及死亡率,其机制可能与阻断T细胞活化的共刺激信号,使Th2反应增强有关.     

Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections

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Calcium-dependent viral internalization is required for adenovirus type 7 induction of IL-8 protein

The host response to adenovirus (Ad) infection involves induction of cytokines in lung epithelia. We have demonstrated induction of the lung neutrophil chemokine interleukin-8 (IL-8) by Ad7, a major lung pathogen, in A549 lung epithelial cells and lung tissue through activation of the Erk signaling pathway. However, the mechanism of IL-8 induction is still unclear. In this paper, we first showed that Ad7 viral gene expression is not essential for IL-8 induction as psoralen-UV inactivation of Ad7 did not affect IL-8 mRNA induction or IL-8 protein induction in A549 cells. We then inhibited internalization of Ad7 by treatment of A549 cells with EGTA in calcium-free medium during exposure to Ad7. We verified that this treatment inhibited Ad internalization by confocal microscopy, FACS analysis and Ad E1A and fiber mRNA expression. Preventing internalization by calcium depletion did not inhibit Erk activation by Ad7. However, calcium-dependent internalization was required for IL-8 protein production in Ad7 exposed cells. This is not likely due to an effect of calcium depletion on downstream Erk signaling or IL-8 protein production since calcium depletion did not block IL-8 protein production stimulated by PMA, and because addition of EGTA subsequent to Ad7 internalization also did not prevent Ad induction of IL-8. These studies indicate that Ad7 internalization is calcium-dependent and is required for IL-8 protein induction upon Ad7 infection. Ad7 induction of Erk is independent of calcium and does not require virus internalization.     

Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes

It remains unclear whether antibody-dependent-enhancement (ADE) of dengue infection merely augments viral attachment and entry through Fcγ receptors or immune complex binding to Fcγ receptors triggers an intrinsic signaling cascade that changes the viral permissiveness of the cell. Using human dengue-immune sera and novel human monoclonal antibodies against dengue in combination with virologic and immunologic techniques, we found that ADE infection increased the proportion of infected primary human monocytes modestly from 0.2% ± 0.1% (no Ab) to 1.7% ± 1.6% (with Ab) but the total virus output markedly from 2 ± 2 (× 10³) FFU to 120 ± 153 (× 10³) FFU. However, this increased virus production was not associated with a reduced secretion of type I interferon or an elevated secretion of anti-inflammatory cytokine, IL-10. These results demonstrate that the regulation of virus production in ADE infection of primary human monocytes is more complex than previously appreciated.     

The KSHV viral interleukin-6 is not essential for latency or lytic replication in BJAB cells

Kaposi's Sarcoma-associated herpesvirus encodes a homolog of the human cellular interleukin-6 that may play a formative role in many KSHV-related diseases. While the viral IL-6 can signal similarly to its human counterpart little is known about the role of vIL-6 during KSHV infection. Using homologous recombination and selection in eukaryotic cells, a KSHV isolate was purified that does not express vIL-6 as was a control recombinant that left vIL-6 intact. The two viruses establish and maintain latency to similar levels in BJAB B-cells, reactivate to similar levels in B-cells and Monkey kidney cells and have very similar KSHV gene expression patterns. BJAB cells expressing KSHV survive better than the parental BJAB cells in low serum and the vIL-6 deletion does not abrogate this growth advantage. Thus vIL-6 is not essential for establishment, maintenance, or reactivation from latency in cell culture and is not involved in the survival of infected BJAB B-cells in low serum.     

IL-10-producing B cells involved in the pathogenesis of Coxsackie virus B3-induced acute viral myocarditis

Background: Interleukin-10 (IL-10)-producing B cells, a subset of regulatory B cells, play critical roles in autoimmune and infectious diseases. However, the role of IL-10-producing B cells in acute viral myocarditis (AVMC) remains unknown. Methods: BALB/c mice were intraperitoneally (i. p.) infected with coxsackievirus B3 (CVB3) to establish AVMC models (AVMC group), while control mice (control group) were treated with phosphate-buffered saline (PBS) i. p. According to the time after injection, the AVMC group mice or control group mice were randomly separated into 1 week and 2 week subgroup. Myocardial histopathological changes were observed by hematoxylin and eosin staining and the frequency of splenic IL-10-producing B cells was measured by flow cytometry. Results: Histopathologic examination of heart tissues showed that mice infected with CVB3 developed AVMC. Compared with control group, the frequency of splenic IL-10-producing B cells was increased significantly in the AVMC group, with the 1 week AVMC subgroup (3.58 ± 0.47%) higher than the 2 week AVMC subgroup (2.50 ± 0.42%) (all P < 0.05). Conclusions: IL-10-producing B cells are increased in CVB3-induced AVMC, indicating that IL-10-producing B cells may play an important role in the pathogenesis of CVB3-induced AVMC.     

IL-33 protects murine viral fulminant hepatitis by targeting coagulation hallmark protein FGL2/fibroleukin expression

Fulminant hepatitis (FH) is characterized by rapid liver failure and high mortality. The pathogenesis of viral FH includes virus-induced immune activation, inflammation, and subsequent hepatic apoptosis and necrosis. However, the mechanisms that underlie FH progression are unclear. IL-33 is a member of the IL-1-related cytokines, considered to be an “alarmin” that participates in various diseases, but its precise role in the coagulation of FH is not very clear. In our study, we found that IL-33 is significantly elevated in mice infected with murine hepatitis virus strain 3 (MHV-3). This is accompanied by an increase in pro-coagulant fibrinogen-like protein 2 (FGL2) in the liver. Previous studies have suggested that an increase in FGL2 is diagnostic of FH and liver necrosis, and animals with no FGL2 had better survivorship during FH. Our studies showed that IL-33 administration in a MHV-3 infection promoted survival during FH, with a significant reduction in FGL2 expression and liver inflammation. In vitro IL-33 treatment abrogated MHV-3 and IFN-γ induced FGL2 expression in RAW264.7 and THP-1 cells, respectively. In conclusion, our research suggests that IL-33 protects against viral fulminant hepatitis in mice by antagonizing expression of the pro-coagulant protein FGL2.     

Early production of IL-17A by γδ T cells in the trachea promotes viral clearance during influenza infection in mice

The innate immune response generated against influenza infection is critical for the inhibition of viral dissemination. The trachea contains different types of innate immune cells that protect the respiratory tract from pathogen invasion. Among them, γδ T cells have the ability to rapidly generate large amounts of pro-inflammatory cytokines to preserve mucosal barrier homeostasis during infection. However, little is known about their role during the early phase of influenza infection in the airways. In this study, we found that, early after infection, γδ T cells are recruited and activated in the trachea and outnumber αβ T cells during the course of the influenza infection that follows. We also showed that the majority of the recruited γδ T cells express the Vγ4 TCR chain and infiltrate in a process that involves the chemokine receptor CXCR3. In addition, we demonstrated that γδ T cells promote the recruitment of protective neutrophils and NK cells to the tracheal mucosa. Altogether, our results highlight the importance of the immune responses mediated by γδ T cells.