Protection against plague following immunisation with microencapsulated V antigen is reduced by co-encapsulation with IFN-gamma or IL-4, but not IL-6

We have investigated intranasal delivery of novel vaccines for plague, based on poly-L-lactide (PLLA) microencapsulated recombinant V antigen (rV) of Yersinia pestis. Microspheres containing rV alone or co-encapsulated with the cytokines IFN-gamma, IL-4 or IL-6 were administered in a two-dose regimen and antibody responses and protective efficacy were monitored. All treatment groups stimulated high rV-specific antibody titres in serum, predominantly of the IgG1 isotype, which were maintained over several months. There was evidence of both IgG and IgA responses in lung samples from all groups. Formulations based on rV antigen alone or rV co-encapsulated with IL-6 provided complete protection against systemic challenge with Y. pestis strain GB; however protective efficacy was impaired by co-encapsulating either IFN-gamma or IL-4 with rV.     

Activation of bovine neutrophil functions by interferon-gamma, tumour necrosis factor-alpha, and interleukin-1 alpha

Neutrophils are the first line of defence against microbial infections. They are important in protecting the bovine mammary gland against environmental and pathogenic bacteria such as Escherichia coli and Staphylococcus aureus. Neutrophils in the peripheral blood of healthy cows are functionally a heterogeneous population of cells with markedly varied phagocytic and oxidative activities. Several cytokines have been found to augment leucocyte functions in humans and animal studies. Therefore, the main objective of the present study was to determine if recombinant human interleukin-1 alpha (rhIL-1 alpha), tumour necrosis factor-alpha (rhTNF-alpha), and interferon-gamma (rhIFN-gamma) would potentiate the functional activity of bovine blood neutrophils, thereby providing a possible means to manipulate the resistance of cows to microbial infections.Neutrophils were isolated from the peripheral blood of nine Holstein-Friesian heifers, with a purity of 89%–96% and viability greater than 98%. Aliquots of neutrophils were incubated with five concentrations of rhIL-1 alpha (0.001–10 ng/ml), rhTNF-alpha (0.5–1000 ng/ml), and rhIFN-gamma (0.01-100 ng/ml) at 37°C for 1 h. Then, fluorescein-labelled opsonised zymosan particles were added and the neutrophil suspensions were incubated further for 30 min to evaluate phagocytic activity by fluorescence microscopy. Similarly, unlabelled opsonised zymosan particles and nitroblue tetrazolium (NBT) were added and incubation was carried out for 15 min to evaluate oxidative activity by a spectrophotometric method. Chemotactic activity of cytokine-treated neutrophils for E. coli lipopolysaccharide-activated fetal calf serum was evaluated using a modified Boyden chamber method. The results showed that pretreatment of neutrophils with various concentrations of each cytokine enhanced their phagocytic and NBT reductive activities but reduced chemotactic activity. The phagocytic and NBT reductive activities increased significantly (p0.05) with an increase in the concentration of the cytokines.     

成人型复发性呼吸道乳头状瘤病的综合治疗

目的:探讨成人型复发性呼吸道乳头状瘤病(adult-onset recurrent respiratory papillomatosis,Ao-RRP)的有效治疗方法。方法:回顾性分析1992-2004年32例成人型复发性呼吸道乳头状瘤病,根据病情分别采取支撑喉镜下钳除或激光切除术、喉造瘘口激光切除术及喉小部分切除 声带I期成形术,9例术后给予系统的干扰素治疗。结果:32例中伴中、重度不典型增生者11例,恶变者5例(恶变率为15．6％);28例术后拔除气管套管,拔管率87．5％,随访1年以上未见复发。全部病例恢复吞咽和发音功能。结论:成人型复发性呼吸道乳头状瘤病有恶变倾向,应根据病情选择相应的治疗方式:喉造瘘口激光切除术适用于反复复发或病变范围较大的病例,喉小部分切除 声带I期成形术适于伴有中、重度不典型增生或已恶变者;术后联合干扰素治疗可抑制或延缓复发。     

Activation of Intestinal Mucosal Immunity in Tumor-bearing Mice by Lactoferrin

We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly increases CD4⁺ and CD8⁺ T cells and NK (asialoGM1⁺) cells in the blood of tumor-bearing mice and enhances anti-metastatic activity. In this paper, we document that oral administration of bLF and bLF-hydrolysate (bLFH) is associated with strong increases in CD4⁺ and CD8⁺ T, as well as asialoGM1⁺ cells in lymphoid tissues and lamina propria of the small intestine in mice, especially in tumor-bearing animals in which Co26Lu cells were implanted subcutaneously. Moreover, IgM⁺ and IgA⁺ B cells in lamina propria of the small intestine were also significantly increased by bLF and bLFH. Bovine apo-transferrin (bTF) did not exhibit such activity. In the colon, only CD8⁺ cells were significantly increased by treatment with bLF, while asialoGM1⁺ cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1⁺ cells. Administration of bLF and bLFH, but not bTF, increased production of interleukin-18 (IL-18), interferon-gamma (IFN-γ) and caspase-1 in the mucosa of the small intestine. Particularly high levels of IL-18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, but not bTF, induced IFN-γ presenting cells in the small intestine. Caspase-1, which processes proIL-18 to mature IL-18, was also induced in the epithelial cells of the small intestine following treatment with bLF and bLFH, but not with bTF. These results suggest that enhanced production of IL-18 and IFN-γ and caspase-1 induction by treatment with bLF may be important for elevation of intestinal mucosal immunity.     

结核病临床诊治进展年度报告（2013年）（第一部分 结核病临床诊断）

近一年来,结核病的诊断方面继续深入进行相关方面的研究,取得了不少进步.在细菌学诊断方面,使用新技术如新型移动数字化荧光显微镜痰检涂片技术可清晰显示并保存图像,发光二极管（LED）性能的荧光显微镜（FM）检查能够明显缩短常规涂片的染色时间,明显提高检出率.影像学诊断在结核病诊断的难点方面进行了详细的研究,如肺癌合并肺结核的临床分期、耐多药结核病与非结核分枝杆菌病的鉴别等.γ干扰素释放试验诊断结核分枝杆菌感染具有很大优势,今年对其诊断价值进行再评价.分子生物学诊断发展迅速,继续对XpertMtb/RIF诊断系统进行深入研究,超支化滚环扩增（hyperbranched rolling circle amplification,HRCA）技术简单、经济、省时,在贫困地区具有广泛的应用前景.介入诊断方面,将气管镜、腔镜技术与分子生物学、超声引导技术、细菌学、病理学检测技术相结合,使得结核病的诊断效率得到显著的提高,如气管镜下支气管冲洗液进行XpertMtb/RIF的检测等.病理学诊断方面以分子病理技术的发展较引人注目,使用活检标本行基因检测提高了结核病的检出率.     

Six-month therapy with aerosolized interferon-gamma for refractory multidrug-resistant pulmonary tuberculosis

The aim of this study was to investigate the adjuvant effects of interferon-gamma (IFN-gamma) inhalation therapy for six months in the treatment of refractory multidrug-resistant pulmonary tuberculosis (MDR-TB). Aerosolized IFN-gamma was given to six MDRTB patients with persistent positive smears and cultures despite long-term medical treatment. The patients received aerosolized two million international units of IFN-gamma three times a week for 6 months while they continued on identical antituberculous chemotherapy. Before IFN-gamma inhalation therapy, the patients received a median of 6.5 (range, 4 to 7) antituberculous drugs for median duration of 29 months (range,7 to 76). After IFN-gamma inhalation therapy, sputum smears remained persistently positive in all patients throughout the study period. Sputum cultures were transiently negative at the 4th month in two patients, but became positive again at the end of 6 months of IFN-gamma therapy. Five patients had radiological improvement including three patients who showed a decrease in the size of the cavitary lesions. Resectional surgery could be performed in one patient in whom substantial clinical and radiological improvement was noted after IFN-gamma inhalation therapy. These results suggest that IFN-gamma inhalation therapy may be effective for some cases of refractory MDR-TB who are otherwise not responding to conventional therapy.     

Hematopoietic stem cell transplantation for complete IFN-gamma receptor 1 deficiency: a multi-institutional survey

OBJECTIVES: To evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in a series of patients with inherited complete IFN-gamma receptor 1 (IFNgammaR1) deficiency. STUDY DESIGN: We report 8 patients who received altogether 11 HSCT from family donors, including 10 HLA-identical (5 siblings and 5 relatives) and 1 HLA-haplo-identical donors. Five grafts were T-cell depleted, and conditioning regimens varied in intensity. RESULTS: Four patients died within 8 months after HSCT. Two of these deaths were due to specific complications related to mycobacterial infection. There was no or very low (2%) donor cell engraftment in 2 survivors. Only 2 patients are in full remission of mycobacterial disease 5 years after HSCT. These are the only patients who received non-T-cell-depleted grafts from an HLA-identical sibling after a fully myeloablative conditioning regimen. CONCLUSIONS: HSCT can lead to prolonged remission of mycobacterial disease in children with complete IFNgammaR1 deficiency. However, optimal control of mycobacterial infection before HSCT and the use of a non-T-cell-depleted transplant from an HLA-identical sibling after a fully myeloablative conditioning regimen are recommended.     

β防御素-2和γ干扰素在尖锐湿疣皮损中表达的研究

目的:研究和探讨β防御素-2(HBD-2)和γ干扰素(IFN-γ)在尖锐湿疣发病和预后中的作用.方法:用免疫组化法检测HBD-2和IFN-γ在25例尖锐湿疣(CA)(初发患者)皮损、20例寻常性银屑病皮损以及25例健康人皮肤石蜡切片中的表达.SPSS 16.0统计软件进行数据分析,组间行Wilcoxon秩和检验,并进行相关性分析.结果:HBD-2、IFN-γ在尖锐湿疣皮损的表达主要见于基底层, HBD-2、IFN-γ水平明显低于银屑病阳性对照组(Z=-7.174,-7.230;P<0.O1),HBD-2的水平较正常皮肤为高表达(Z=-5.147,P<0.01), IFN-γ的水平较正常皮肤为低表达(Z=-6.311,P<0.05),且HBD和IFN无相关性(r=0.123,P=0.467>0.01).结论:推测HBD-2、IFN-γ可能通过不同的途径共同参与了尖锐湿疣的免疫反应过程并发挥了一定的作用.