Melatonin induces changes to serum cytokines in mice infected with the Venezuelan equine encephalomyelitis virus

We determined the influence of melatonin (MLT) on the induction of interleukin (IL)-2, IL-1 beta, IL-4, tumour necrosis factor-alpha (TNF-alpha) and gamma interferon (IFN-gamma) on mice infected with the Venezuelan equine encephalomyelitis (VEE) virus. Levels of IFN-gamma in the MLT-treated group were significantly increased (P < 0.001) when compared with the control non-infected group from day 1 to 6 post-infection (p.i.), while in infected mice treated with 500 micrograms MLT/kg of bodyweight enhanced levels of IFN-gamma were evident from 4 to 6 days p.i. No differences were detected in the levels of IL-2 between the controls, the infected mice treated with MLT and the infected untreated group, from day 2 p.i. No changes in serum levels of IL-4 were detected. In infected mice treated with MLT, blood levels of IL-1 beta were elevated almost 10-fold from day 1 to day 6 p.i. when compared to the control, the infected and the non-infected MLT-treated mice (P < 0.001). A highly significant rise (P < 0.001) of TNF-alpha was found in infected mice treated with MLT, from day 1 to 6 p.i. when compared to the other groups. A significant rise (P < 0.001) was also evident in the infected non-MLT-treated group and a less pronounced rise in the non-infected mice treated with MLT when compared to controls. The blockade of IFN-gamma and TNF-alpha did not inhibit the protective effect of MLT but when IL-1 beta was neutralized, 100% of the infected mice died suggesting that IL-1 beta induced by MLT treatment is a target cytokine to generate an immune response against the viral infection.     

Protective activity of recombinant cytokines against Sendai virus and herpes simplex virus (HSV) infections in mice

The efficacy of recombinant cytokines such as murine interferon-gamma (IFN-gamma), human granulocyte colony-stimulating factor (G-CSF), mouse granulocytic-macrophage colony-stimulating factor (GM-CSF) and human interleukin-1 beta (IL-1 beta) has been examined for augmentation of host resistance against Sendai virus and herpes simplex virus (HSV) infections. All four cytokines were found to protect mice against Sendai virus infection. IFN-gamma afforded protection when administered intranasally but not intravenously several days before the infection. Intranasal administration of G-CSF one day before the infection was the most effective administration route and timing. Intranasal administration of GM-CSF was found to afford protection 1 or 3 days before the infection. IL-1 beta demonstrated therapeutic activity against Sendai virus infection after intranasal administration on the same day as the infection. When each of the cytokines was administered subcutaneously four times daily into cyclophosphamide-treated mice before intravenous infection with HSV, only GM-CSF revealed any protective activity.     

Gene gun mediated vaccination is superior to manual delivery for immunisation with DNA vaccines expressing protective antigens from Yersinia pestis or Venezuelan Equine Encephalitis virus.

Plasmids expressing the V antigen of Yersinia pestis or the E2 glycoprotein of Venezuelan Equine Encephalitis (VEE) virus were used to vaccinate mice by intra-dermal or intra-muscular injection, or by particle-mediated bombardment using the Helios gene gun. After two immunizations, groups of mice which had received 4 microg doses of plasmid DNA using the gene gun had IgG levels which were higher than in other groups manually immunised with 12-fold more plasmid DNA. The immunoglobulin isotype profile was predominantly IgG1 following inoculation with either plasmid. Our results indicate that gene gun mediated vaccination can be used to increase the magnitude of the immune response to both bacterial and viral antigens expressed by plasmid DNA.     

帕拉米韦对流感病毒感染小鼠免疫功能及炎症反应的调节作用

目的探究帕拉米韦对流感病毒感染小鼠免疫功能及炎症反应的调节作用。方法将48只BALB/c小鼠随机分为对照组、感染组、低、高剂量治疗组,每组12只,病毒感染组、低、高剂量治疗组小鼠用H1N1病毒株(PR8)滴鼻途径攻毒,4 h后治疗组小鼠通过肌肉注射帕拉米韦4、20 mg/kg·d,连续注射5 d,对照组和病毒感染组给予等量生理盐水;在攻毒后3 d时,每组随机取2只小鼠处死,观察肺组织病理变化及其病毒载量;攻毒后5 d时,每组随机取6只小鼠处死,取脾制成单细胞后,利用流式细胞仪检测T淋巴细胞亚群水平,取肺组织制成组织匀浆,利用酶联免疫吸附法(ELISA)检测白细胞介素-2(Interleukin-2,IL-2)、IL-6、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、干扰素-γ(interferon-γ,IFN-γ)水平,每日观察小鼠状态,持续观察14 d,根据观察结果分析小鼠的存活率及平均生存时间。结果攻毒14 d后,感染组小鼠全部死亡,死亡率明显高于低、高剂量治疗组(P<0.05),低剂量治疗组的死亡率高于高剂量治疗组(P<0.05);攻毒后3 d时,低、高剂量治疗组小鼠的肺指数及肺组织病毒载量低于感染组(P<0.05),高剂量治疗组上述指标变化更显著(P<0.05);感染组小鼠肺组织的病理损伤及炎症浸润严重,低、高剂量治疗组小鼠的病理损伤及炎症浸润有不同程度减轻,且高剂量治疗组改善更明显;攻毒后5 d时,低、高剂量治疗组小鼠的CD₄⁺、CD₄⁺/CD_₈⁺、IL-6、TNF-α水平低于感染组,IL-2、IFN-γ水平高于感染组(P<0.05),且高剂量治疗组的IL-6、TNF-α水平低于低剂量治疗组,IL-2、IFN-γ水平高于低剂量治疗组(P<0.05)。结论帕拉米韦通过抑制肺组织中流感病毒的释放和增殖,缓解过度免疫反应引起的炎症损伤,进而提高小鼠存活率。     

Venezuelan equine encephalitis virus vectors expressing HIV-1 proteins: vector design strategies for improved vaccine efficacy

A live virus vaccine vector has been constructed from a molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE). High levels of foreign protein expression are regulated by an additional copy of the 26 S viral subgenomic RNA promoter. The position of this additional promoter and foreign gene in the VEE genome was predicted to have a major influence on expression level of the heterologous protein. Two sites in the genome were tested to determine the optimal site for expression of the matrix/capsid (MA/CA) coding region of human immunodeficiency virus (HIV-1). One vector contained the additional promoter and the MA/CA genes immediately downstream of the VEE E1 gene at the 3' end of the genome. In the second vector, the additional promoter was introduced immediately upstream from the authentic 26 S subgenomic promoter. Significantly higher levels of MA/CA were expressed from the downstream vector compared to the upstream vector. However, the stability of expression for both vectors was similar following passage in baby hamster kidney cells (BHK) cells. In BALB/c mice, the two vectors elicited similar levels of cellular immune responses to MA/CA as determined by bulk cytotoxic T-lymphocyte assays and precursor frequency analysis, but the humoral response induced by the downstream vector was significantly stronger. At 11 months post boosting with the downstream vector, serum antibody levels against HIV MA/CA were undiminished, and MA/CA specific CTLp were detectable in all mice tested. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins.     

IL-6 induces long-term protective immunity against a lethal challenge of influenza virus

The coadministration of cytokines can modulate immunity in DNA based viral vaccines. In order to determine the effects of various cytokines on long-term protection against the influenza virus, mice were intramuscularly coinoculated with plasmids that encoded either the granulocyte-macrophage colony-stimulating factor (GMCSF), interleukin-4 (IL-4), interleukin-12 (IL-12), or the interleukin-6 (IL-6) gene, in the presence of two plasmids that encoded the nucleoprotein (NP) and the hemagglutinin (HA) gene of the influenza A virus. The coadministration of IL-4, IL-6 and IL-12 transiently enhanced antibody responses against influenza virus in early time points (4 to 7 week post immunization) after post inoculation. The expression of GMCSF gene resulted in the sustained elevation of antibody responses for at least 20 weeks post inoculation. However, NP-specific CTL responses decreased in these animals. Mice that received either the IL-12 or the IL-6 gene had enhanced NP-specific CTL responses. Remarkably, the coadministration of the IL-6 gene completely protected mice from a lethal challenge with influenza virus. Conversely, mice that received the IL-4 gene appeared to be more susceptible to lethal challenge than mice that were inoculated with the NP and the HA genes alone. These results demonstrate that the use of cytokines as molecular adjuvants when coadministered in influenza DNA vaccination must be specific. Our data also demonstrates that the coadministration of IL-6 should be considered to enhance the efficacy of influenza DNA vaccines.     

Potential for Central American mosquitoes to transmit epizootic and enzootic strains of Venezuelan equine encephalitis virus.

Experimental studies were undertaken to compare the vector competence of Culex (Melanoconion) taeniopus Dyar and Knab, Culex (Melanoconion) ocossa Dyar and Knab, and Psorophora confinnis (Lynch Arribalzalga) from Central America for epizootic (IAB) and enzootic (IE) strains of Venezuelan equine encephalitis (VEE) virus. Virus infection and dissemination rates were significantly higher in Cx. taeniopus orally exposed to IE as compared to those orally exposed to IAB virus. In contrast, both infection and dissemination rates were similar in Cx. ocossa exposed to either IAB or IE strains of VEE virus. Thus, susceptibility to epizootic and enzootic strains of VEE virus seems to be species specific within the subgenus Culex (Melanoconion). Both species transmitted each strain of VEE virus after intrathoracic inoculation, indicating that a midgut barrier affected vector competence in these species. Psorophora confinnis was equally susceptible to both IAB and IE viruses, but apparently had a salivary gland barrier, as only 1 of 16 mosquitoes with a disseminated infection transmitted VEE virus by bite.     

Enhancing effects of immunoactive peptide FR48217 on immunological responses to vaccination by inactivated influenza virus

The adjuvant effect of an immunoactive peptide, FR48217 (FR), was investigated in mice vaccinated with inactivated influenza virus with and without FR (designated as V + FR and V - FR, respectively). Mice were infected with influenza virus A/PR/8/34 28 days after vaccination. The survival rate indicated a strong adjuvant effect of FR on vaccination with inactivated influenza virus. No difference in interferon activity in the pulmonary lavage fluid was found between the V + FR and V - FR groups. The titres of virus-specific IgA and IgG antibodies in the serum increased after vaccination in both V + FR and V - FR groups and were significantly higher in the V + FR group than in the V - FR group. On days 2 and 4 after viral infection, the serum antibody titres decreased sharply and then increased again rapidly. The free IgA and IgG antibody levels in the pulmonary lavage fluid of vaccinated mice started to increase after day 4. It is proposed that one of the mechanisms by which FR has the adjuvant effect on vaccination is the increase of virus-specific IgA and IgG antibodies in the serum, which are diffused into the infection sites of the epithelial tissues in the respiratory tract to neutralize the virus at the early stages of viral infection.     

Infection of young adult mice with dengue virus type 2

Young adult female mice, five to six weeks old, were injected intraperitoneally with 2·5 × 10^6·3 LD₅₀ of dengue-2 virus, New Guinea C strain. The mice were killed on day 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28 and 35 respectively. By means of the immunofluorescent antibody technique, viral antigen appeared as irregular granules in the reticuloendothelial cells of liver, lymph nodes and spleen of infected mice on the first day after inoculation and then diminished. From the fifth to sixth day of infection dengue antigen appeared again as homogeneous staining in the cytoplasm of single or groups of mononuclear cells in the lymphatic sinuses only. Later, by the third week of infection, dengue antigen could be seen in the mononuclear cells located in the marginal zone of lymphoid follicle of the spleen, the pattern of staining changing to bright spherical granules. At the same time, the deposition of immune complexes (composed of dengue antigen, mouse gamma and β1C globulin) could be seen in the renal glomeruli of infected mice.Serum antibody to dengue virus was found at low levels, being maximal on the 14th day after infection. Dengue virus was not isolated from the sera or from the infected organs. Granulomatous inflammation developed in lymph nodes and liver of mice infected with dengue virus and in mice inoculated with normal mouse brain suspension. Proliferative glomerular lesion was observed on day 14 after inoculation without definite abnormal urine findings.     

A novel combination treatment of armed oncolytic adenovirus expressing IL-12 and GM-CSF with radiotherapy in murine hepatocarcinoma

In this study, a novel combination treatment of armed oncolytic adenovirus expressing interleukin 12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiation was investigated for antitumor and antimetastatic effect in a murine hepatic cancer (HCa-I) model. Tumor bearing syngeneic mice were treated with radiation, armed oncolytic virus Ad-ΔE1Bmt7 (dB7) expressing both IL-12 and GM-CSF (armed dB7), or a combination of both. The adenovirus was administered by intratumoral injection 1 × 10(8) PFU per tumor in 50 μl of PBS four times every other day. Tumor response to treatment was determined by a tumor growth delay assay. Metastatic potential was evaluated by a lung metastasis model. To understand the underlying mechanism, the level of apoptosis was examined as well as the change in microvessel density and expression of immunological markers: CD4+, CD8+ and Cd11c. The combination of armed dB7 and radiation resulted in significant growth delay of murine hepatic cancer, HCa-1, with an enhancement factor of 4.3. The combination treatment also resulted in significant suppression of lung metastasis. Increase of apoptosis level as well as decrease of microvessel density was shown in the combination treatment, suggesting an underlying mechanism for the enhancement of antitumor effect. Expression of immunological markers: CD4+, CD8+ and Cd11c also increased in the combination treatment. This study showed that a novel combination treatment of radiotherapy with armed oncolytic adenovirus expressing IL-12 and GM-CSF was effective in suppressing primary tumor growth.     

肠道菌群失调对流感病毒感染小鼠急性肺损伤的影响

目的 探讨肠道菌群失调对流感病毒感染小鼠急性肺损伤的影响及作用机制。方法 BALB/c小鼠随机分为正常对照组、流感病毒对照组、甲硝唑模型组,每组12只。甲硝唑模型组小鼠用甲硝唑（18 mg/mL）连续灌胃8 d,于d9滴鼻甲型流感病毒A/PR/8/4稀释液（103pfu/鼠）,构建肠道菌群失调小鼠感染流感病毒的模型。观察各组小鼠肺组织及盲肠的病理变化,检测肺组织中脂多糖LPS及炎性相关因子肿瘤坏死因子 - α（Tumor necrosis factor - α,TNF - α）、白介素 - 1β（Interleukin - 1β, IL - 1β）、白介素 - 6（Interleukin - 6,IL - 6）、干扰素 - β（Interferon - β,IFN - β）水平,并采用免疫组织化学染色法定位肺组织Toll样受体4（Toll - like receptor 4, TLR4）表达情况。结果 甲硝唑模型组小鼠肺及盲肠组织炎症损伤和病理改变情况较比病毒对照组更加严重,同时小鼠肺组织中LPS含量显著增加,差异有统计学意义（P＜0.05）,TNF - α、IL - 1β、IL - 6、IFN - β水平明显升高（P＜0.05）。TLR4在甲硝唑模型组小鼠肺组织中的表达明显高于病毒对照组,差异有统计学意义（P＜0.05）。结论 肠道菌群失调引起LPS/TLR4通路激活,从而上调小鼠肺组织流感病毒所致的炎性风暴,进一步加重流感病毒引起的组织病理改变。     

Vitamin D down-regulates the expression of some Th17 cell-related cytokines,key inflammatory chemokines,and chemokine receptors in experimental autoimmune encephalomyelitis

Objectives: A spectrum of immunomodulatory properties was attributed to vitamin D (VD). Here, the VD effects on expression of some Th17 cell- related cytokines, chemokines and chemokine receptors were investigated in experimental autoimmune encephalomyelitis (EAE).

Methods: One group of C57BL/6 mice, considered as healthy group, was treated with phosphate buffered saline (PBS). EAE was induced in other three groups and treated from day +3 to +30 with PBS, olive oil (VD vehicle) or 200 ng of VD. At day 31, the expression of interleukin-17 (IL-17), IL-23, chemokine (C-C motif) ligand 20 (CCL20), CCL22, CC chemokine receptor 4 (CCR4) and CCR6 in spinal cord and serum IL-17 and IL-23 levels were measured by real-time PCR and ELISA, respectively.

Results: The expression of IL-17, IL-23 P19, IL-23 P40, CCL20, CCL22 and CCR4 in spinal cord and serum IL-17 and IL-23 levels in PBS-administrated EAE mice were significantly increased compared with healthy group. In EAE mice treated with VD, the expression of aforementioned parameters was significantly reduced in comparison with PBS-administrated EAE mice.

Conclusion: VD down-regulates the expression of some inflammatory cytokines, chemokines and chemokine receptors in EAE mice. The possible therapeutic potential of VD in multiple sclerosis can be considered in future investigation.     

慢性乙型肝炎患者外周血中树突状细胞的分离、纯化与扩增

目的探讨从慢性乙型肝炎(CHB)患者外周血中分离、纯化与扩增树突状细胞(DC)的有效方法。方法分别从健康自愿者(10例,对照组)和CHB患者(10例,实验组)外周血中分离出单核细胞(Mo),然后将实验组的Mo与GM-CSF、IL-4共同培养,于倒置显微镜下观察计数细胞,以流式细胞仪检测培养前、后的DC数量及其表面CD40、CD80、CD86和MHC-DR的表达水平,并与对照组比较。结果与对照组相比,实验组DC表面CD40、CD80、CD86和MHC-DR表达水平较低(P<0.01);经GM-CSF、IL-4联合培养5d后,其Mo中的DC数较培养前明显增多(P<0.01),且DC表面CD40、CD80、CD86和MHC-DR表达水平较培养前明显增高(P<0.01),与对照组相比则无明显差异(P>0.05)。结论GM-CSF、IL-4联合应用能有效地从CHB患者外周血中制备出大量具有功能活性的DC。     

Low-dose gamma-rays and simulated solar particle event protons modify splenocyte gene and cytokine expression patterns

The goal was to investigate the T helper (Th) response in splenocytes of mice exposed to low-dose/low-dose-rate (LDR) γ-rays, simulated solar particle event protons (sSPE), or combination of both. C57BL/6 mice were exposed to LDR γ-radiation ((57)Co) to a total dose of 0.05 Gray (Gy) at 0.024 cGy/h, either with or without subsequent exposure to 2 Gy sSPE protons. Expression of genes related to Th cells was evaluated immediately after exposure (day 0). On day 21, intra- and extracellular cytokine production was assessed after activation with anti-CD3 monoclonal antibodies (mAb) or phorbol 12-myristate 13-acetate/ionophore (PMA/I). Five genes were significantly modulated on day 0 in one or more of the irradiated groups compared to controls (p < 0.05): Ccl11, Ccr5, Cd80, Inha, and Il9. On day 21, numbers of cells positive for interferon-γ were high in the LDR + sSPE group versus 0 Gy and LDR γ-rays (p < 0.05), but there was no difference in IL-2 and TNF-α. Levels of secreted cytokines after anti-CD3 mAb activation were high for 5 (MIP-1α, GM-CSF, IFN-γ, TNF-α, IL-13) and low for 2 (IL-7, IL-9) in all irradiated groups. Priming with LDR photons had a significant effect on IFN-γ and IL-17 compared to sSPE protons alone; IL-2 was low only in the LDR + sSPE group. The cytokine patterns after anti-PMA/I activation were different compared to anti-CD3 mAb and with fewer differences among groups. The data show that total-body exposure to space-relevant radiation has profound effects on Th cell status and that priming with LDR γ-rays can in some cases modulate the response to sSPE.     

Cytokine adjuvancy of BVDV DNA vaccine enhances both humoral and cellular immune responses in mice.

The effect of cytokine adjuvancy on a bovine viral diarrhoea virus (BVDV) DNA vaccine expressing the major glycoprotein E2 was investigated in mice. Murine interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were chosen for their potential ability to enhance the humoral and cellular immune responses involved in protection against BVDV. Both cytokines, co-administered as separate plasmid constructs, had a marked effect on ELISA and neutralising antibody titres, improving the spectrum of neutralisation induced by the E2 DNA vaccine, as demonstrated in heterologous neutralisation assays. The predominance of IgG2a isotypes, in sera from all DNA injected groups, indicated a Th1 biased immune response. Antigen specific proliferation of murine splenocytes from immunised mice was enhanced by cytokine co-administration, with the highest stimulation indexes observed in the group co-injected with the GM-CSF construct. These results obtained in the mouse (Balb/c; H2-kd) animal model demonstrate the value of the two cytokines as adjuvants for the E2 DNA vaccine. The need for an adjuvant in this system was emphasised by the MHC restriction observed when C57BL/6 mice (H2-kb) were immunised with the E2 DNA construct. Antibody levels were dramatically lower in this mouse strain.     

GM-CSF在小鼠阴道假丝酵母菌感染中作用的研究

目的 通过对阴道假丝酵母菌小鼠模型血液和阴道灌洗液中粒细胞-巨噬细胞集落刺激因子在感染过程中的含量变化研究以及重组人粒细胞-巨噬细胞集落刺激因子对模型的干预,探讨粒细胞-巨噬细胞集落刺激因子在小鼠阴道假丝酵母菌感染中的作用.方法 构建1次感染和2次感染阴道假丝酵母菌病小鼠模型,在感染后的第2、7和14天检测小鼠血液和阴道灌洗液中粒细胞-巨噬细胞集落刺激因子含量.并给予斯皮仁诺灌胃或重组人粒细胞-巨噬细胞集落刺激因子腹腔注射,连用3天后行阴道灌洗液菌落形成单位计数.结果 无论是1次感染还是2次感染的小鼠,阴道灌洗液及血液中粒细胞-巨噬细胞集落刺激因子含量在感染后的第7天最高,分别为207.50±29.64pg/mL和251.25±41.12pg/mL,经两组对比分析,感染后第2天、第7天、第14天t值分别为3.024、2.255、2.345,均P＜0.05.对感染后的相同时间进行比较,接受2次感染的小鼠,其阴道灌洗液及血液中粒细胞-巨噬细胞集落刺激因子含量比接受1次感染小鼠的含量均增高,且阴道灌洗液中的含量高于血液中含量.接受斯皮仁诺灌胃的小鼠均被治愈,接受重组人粒细胞-巨噬细胞集落刺激因子腹腔注射的8只小鼠中有6只治愈.粒细胞-巨噬细胞集落刺激因子在对照组阴道灌洗液中含量极微小,在血液中的含量均低于感染组.结论 粒细胞-巨噬细胞集落刺激因子在对抗阴道假丝酵母菌感染中起保护作用,特别是对于2次感染,且局部作用大于系统作用.重组人粒细胞-巨噬细胞集落刺激因子对该疾病有一定的治疗效果,可考虑其作为一种新的辅助治疗.     

Expression, processing, and immunogenicity of the structural proteins of Venezuelan equine encephalitis virus from recombinant baculovirus vectors

Recombinant baculoviruses expressing the structural proteins of Venezuelan equine encephalitis virus (VEE) have been constructed and the intracellular processing, antigenicity, and immunogenicity of the expression products have been assessed. Baculoviruses expressing the entire structural protein region (C-E3-E2-6K-E1), or the complete glycoprotein region (E3-E2-6K-E1), generated products in Sf9 cells that were accurately and completely processed, and resulted in mature proteins that were antigenically and electrophoretically indistinguishable from authentic viral proteins. These products were highly immunogenic in BALB/c mice, induced efficient VEE neutralizing responses, and protected these animals against challenge with virulent VEE. Expression of individual glycoprotein regions (E3-E2 and 6K-E1) generated products that were accurately but incompletely processed, and induced non-neutralizing antibodies that reacted more efficiently with denatured than native VEE proteins. Nonetheless, immunization with the 6K-E1 expression product provided complete protection against VEE challenge.     

rhIL-18对辐照小鼠免疫功能的调节作用

目的研究重组人白细胞介素18(rhIL-18)对辐照小鼠免疫功能的调节作用,探讨rhIL-18在辐照防护中的应用价值。方法将32只小鼠随机分为正常对照组、单纯辐射照射组、rhIL-18+辐射照射组、辐射照射+rhIL-18组,辐照剂量为60Coγ射线4.0Gy,rhIL-18为0.6mg腹腔注射,处理后分别用淋巴细胞转化实验、NK细胞毒实验、T淋巴细胞亚群检测,测定小鼠脾细胞体外培养上清中白细胞介素-2(IL-2)、γ-干扰素(IFN-γ)、单核巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)和血清中IgG的含量,观察rhIL-18对其免疫功能的调节作用。结果与单纯辐射照射组比较,rhIL-18能提高辐照后小鼠的T、B淋巴细胞转化能力(P0.05),使T、B淋巴细胞转化能力恢复或超过正常对照组水平,辐射照射后注射rhIL-18组的刺激指数达到了2.9〔刀豆蛋白A(ConA)组〕和6.1〔脂多糖(LPS)组〕;可促进辐照所致NK细胞活性抑制的恢复(P0.05),使NK细胞对肿瘤细胞杀伤率达到21.8%～35.6%;上调CD4T细胞数量,达到50个/ml(P0.05),提高辐照小鼠脾细胞分泌IFN-γ、GM-CSF和IL-2的能力(P0.05),但对IL-4分泌能力和IgG产生能力没有调节作用。结论rhIL-18具有促进辐照小鼠免疫功能恢复的作用。     

禽流感病毒免疫血清对实验感染小鼠的紧急预防效果研究

目的 评价H5N1亚型禽流感病毒免疫血清对实验感染小鼠的紧急预防保护效果.方法 给30只小鼠腹腔注射0.2 ml/只禽流感病毒免疫血清,注射后1～19 d内每天采3只小鼠血清测定血凝抑制(HI)抗体效价,测定免疫血清在小鼠体内的消长规律;给10只小鼠腹腔注射1.5 ml/只禽流感病毒免疫血清,检测免疫血清对小鼠的安全性;将70只小鼠按数字表法随机分为7组,分别为正常对照组、病毒对照组以及免疫血清高剂量早期组、高剂量中期组、高剂量晚期组、中剂量组、低剂量组.每组10只,分别在攻毒前8 d,4 d和1 d时腹腔注射血清0.2 ml/只、0.1 ml/只、0.05 ml/只禽流感病毒免疫血清,然后给小鼠滴鼻感染10个半数致死量(LD50)病毒,攻毒后连续观察14 d,计算小鼠存活率和平均存活天数,比较各实验组小鼠肺指数及肺脏病毒感染滴度.结果注射0.2 ml免疫血清小鼠HI抗体效价在1～15 d时为26,在17 d以后开始下降;1.5 ml免疫血清注射小鼠全部存活,没有发病;在攻毒前8 d、4 d和1 d时给小鼠腹腔注射0.2 ml免疫血清,小鼠存活率分别为80%、100%和100%,平均存活天数分别为13.1 d、14.0 d和14.0 d,在攻毒前1 d给小鼠腹腔注射0.1 ml和0.05 ml免疫血清,小鼠存活率分别为100%和50%,平均存活天数分别为14.0 d和11.7 d,各实验组小鼠肺指数(O.0096±0.0033～0.0145±0.0060)均小于病毒对照组(0.0199±0.0025),除低剂量组外,均具有统计学意义(P值0.0022～0.0470,＜0.05),各实验组小鼠肺脏病毒滴度(TCID50)较病毒对照组平均低2个滴度.结论禽流感病毒免疫血清对实验感染小鼠具有较好的紧急预防保护效果,可作为人禽流感紧急预防制剂加以研究开发.     

Venezuelan equine encephalitis virus, southern Mexico

Equine epizootics of Venezuelan equine encephalitis (VEE) occurred in the southern Mexican states of Chiapas in 1993 and Oaxaca in 1996. To assess the impact of continuing circulation of VEE virus (VEEV) on human and animal populations, serologic and viral isolation studies were conducted in 2000 to 2001 in Chiapas State. Human serosurveys and risk analyses indicated that long-term endemic transmission of VEEV occurred among villages with seroprevalence levels of 18% to 75% and that medical personnel had a high risk for VEEV exposure. Seroprevalence in wild animals suggested cotton rats as possible reservoir hosts in the region. Virus isolations from sentinel animals and genetic characterizations of these strains indicated continuing circulation of a subtype IE genotype, which was isolated from equines during the recent VEE outbreaks. These data indicate long-term enzootic and endemic VEEV circulation in the region and continued risk for disease in equines and humans.