快速诱导人胎脾LAK细胞的实验研究

应用基因重组人干扰素α(IFN-α)体外诱导三株人胃癌细胞系SGC_(7901)、MGC_(803)和MKN_(45),用ABC-CELISA法检测诱导组与对照组细胞表面免疫抑制酸性蛋白Ⅱ型(IAP-2)表达量。制备人脾来源LAK细胞,MTT法检测各组LAK细胞杀伤率。结果表明,在无IFN-α存在的对照组,三株细胞均表达IAP-2,其水平较低,对LAK细胞杀伤敏感。在IFN-α诱导组,当IFN-α<1000U/ml时,三株细胞IAP-2表达量显著高于对照组(P<0.001),而LAK细胞杀伤率显著低于对照组(P<0.005);当IFN-α>1000U/ml时,这些细胞IAP-2表达量显著低于对照组(P<0.005),LAK细胞杀伤率显著高于对照组(P<0.001)。这些结果提示:IFN-α对人胃癌细胞IAP-2表达的调节可能影响癌细胞对LAK细胞杀伤敏感性。     

Common variable immunodeficiency (CVID) and MxA-protein expression in blood leucocytes.

The underlying immunopathogenic mechanism of CVID has been suspected to involve a chronic viral infection or an autoimmune condition. However, formal proof of viral infection is lacking. Measurement of MxA-protein in leucocyte lysates is a sensitive test for evaluating the activation of the host's interferon system. Both viral infections and autoimmune diseases such as systemic lupus erythematosus (SLE) strongly induce MxA-protein in peripheral leucocytes. We therefore examined 15 patients with longlasting hypogammaglobulinaemia for MxA-protein induction in vivo: 13 patients suffered from CVID, one from hyper-IgM syndrome, and one patient had chronic B lymphocytic leukaemia associated with immunoglobulin deficiency and chronic papilloma virus infection (condylomata accuminata). Only the latter patient exhibited a strong MxA-protein expression; two CVID patients were borderline positive, and the remaining 12 patients including the hyper-IgM syndrome were MxA-protein-negative. There was no relationship between MxA expression and low CD4/CD8 ratios or increased CD8/CD57+ T cell counts, although both conditions are often observed in CVID as well as in chronic viral infections. When exposed in vitro to interferon-alpha (IFN-alpha), peripheral blood leucocytes of four MxA-negative patients were capable of producing normal amounts of MxA-protein. Taken together, these results argue against a viral or autoimmune pathogenesis of CVID.     

Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid

Cytokines play an important role in the pathology associated with chronic inflammatory diseases. We measured the total amounts [picograms (pg)] and concentrations (pg/μl) of interleukin-1 alpha (IL-lα), interleukin-8 (IL-8) and interferonalpha (IFN-α) in 20 s gingival crevicular fluid (GCF) samples obtained from 2 diseased and 2 healthy sites in 20 subjects with periodontitis, and from 2 healthy sites in 20 subjects without disease. Both the mean amount and concentration of IL-lα were significantly higher (p < 0.001) in diseased sites compared to healthy sites in subjects with disease. The results for IL-8 and IFN-α differed depending on the method of reporting. Whereas the amount of IL-8 was significantly higher (p < 0.01) in diseased sites, the mean concentration of IL-8 was lower compared to healthy sites. The mean amount of IFN-α was similar in health and disease; however, the concentration of IFN-alpha was significantly lower in diseased sites (p < 0.001) corresponding to the significant increase in crevicular fluid volume (p < 0.001). There were no significant differences in the amount or concentrations of the 3 cytokines between healthy sites from subjects with disease and healthy sites from healthy controls. The total amounts of both IFN-α and IL-8 were correlated between healthy and diseased sites in subjects. These data suggest that, while the disease status of a site is the major determinant of the levels of these cytokines locally, subjects with high levels of IL-8 and IFN-α in healthy sites also tend to have high levels of these cytokines in diseased sites. Finally, both the concentrations and total amounts of IL-8 and IFN-α were significantly correlated in diseased sites, suggesting that levels of these two cytokines rise or fall in tandem. The combination of decreased IL-8 and decreased IFN-α concentrations at diseased sites may reflect the reduced anti-bacterial host defense activity at that site.     

Cutaneous melanoma: interferon alpha adjuvant therapy for patients at high risk for recurrent disease

Systemic adjuvant therapy in melanoma patients is the systemic treatment that is administered with the goal of eradicating micrometastatic deposits in patients who are clinically free of disease after surgical removal of the primary melanoma, but with a high risk of systemic recurrence. Interferon-alpha (IFN-alpha) is one of the most frequently used adjuvant therapies. Several randomized trials evaluated the efficacy of IFN-alpha in melanoma patients. However, results from conducted trials are controversial. Twelve randomized IFN-alpha trials are discussed in detail. All trials, including meta-analysis, failed to demonstrate a clear impact of IFN-alpha therapy on overall survival in melanoma patients. Based on currently available evidence, IFN-alpha therapy in the adjuvant setting should not be considered standard of care for patients who have melanoma. Results from ongoing studies are awaited. Further research for this therapy is required.     

Interferon-alpha and dexamethasone inhibit adhesion of T cells to endothelial cells and synovial cells

We investigated whether interferon-gamma (IFN-gamma), interferon-alpha (IFN-alpha) and glucocorticoids affected the adhesion of T cells to human umbilical endothelial cells or human synovial cells. About 30% of peripheral blood T cells could bind to unstimulated endothelial cells, but only a few T cells could bind to unstimulated synovial cells. When both endothelial cells and synovial cells were cultured with recombinant IFN-gamma (rIFN-gamma), the percentage of T cell binding to both types of cells increased in a dose-dependent manner. rIFN-alpha and dexamethasone blocked the T cell binding to unstimulated endothelial cells. Furthermore, rIFN-alpha and dexamethasone suppressed T cell binding to both endothelial cells and synovial cells stimulated by IFN-gamma, and also inhibited intercellular adhesion molecule-1 (ICAM-1) expression on both endothelial cells and synovial cells stimulated by IFN-gamma. These results suggest that IFN-alpha and glucocorticoids may inhibit T cell binding to endothelial cells or synovial cells by modulating adhesion molecule expression on these cells.     

SOCS1对α干扰素调节乙肝病毒复制作用的影响

目的 研究细胞因子信号阻抑蛋白1(SOCS1)对α干扰素(IFN-α)调节乙型肝炎病毒(HBV)复制作用的影响.方法 HepG2.2.15细胞按处理方法分为3组:空白组(未加IFN-α处理)、对照组(加空质粒转染)、实验组(加pcDNA3.1-SOCS1转染),转染后检测对照组与实验组有质粒表达后,用1 000 IU/...     

慢性丙肝患者干扰素治疗前后血清细胞因子的变化

目的 :探讨细胞因子在慢性丙型肝炎发病机制中的作用。方法:2 0例慢性丙型肝炎患者应用干扰素联合利巴韦林抗病毒治疗 2 4周。于治疗前后用 EL ISA法检测血清 IL- 2、IFN- γ、IL- 4、IL- 10水平 ,同时检测生化和病毒指标并观察不良反应。结果:抗病毒治疗后 IL- 2、IFN- γ、IL- 4、IL- 10水平发生了明显变化。与治疗前比较 ,IL- 2、IFN- γ水平逐渐升高 ,IL- 4、IL- 10水平逐渐降低 ,其中 IL- 2、IL- 10水平变化具有统计学意义 (P<0 .0 1)。对干扰素完全应答者 15例 ,IL- 2、IL- 10水平变化具有统计学意义 (P<0 .0 5 ) ;无应答者 5例 ,IL- 2、IFN- γ、IL- 4、IL- 10水平变化无统计学意义 (P >0 .0 5 )。抗病毒治疗过程中无严重不良反应。 结论:IL - 2、IL - 4、IL - 10、IFN-γ共同参与了丙型肝炎的发病。干扰素联合利巴韦林通过调整机体的免疫状态而发挥抗病毒效应 ,IL - 2、IL - 10可以作为预测抗病毒疗效的指标之一。     

IFNAR2在肾癌中的表达及其临床意义

【目的】探讨干扰素受体IFNAR2与肾癌发生发展的相关性。【方法】对12例肾癌临床资料进行回顾性分析总结;采用RT—PCR技术检测IFNAR2在12例肾癌组织及癌旁组织中的表达模式。【结果】RT—PCR实验结果显示：IFNAR2在癌旁肾组织中3例表达阴性,9例阳性;在12例肾癌组织中全部阳性表达。【结论】推测IFNAR2可能是肾癌发生过程中的一个早期事件,并与肾癌的发生和进展有关,这将可能为肾癌的发病机制、临床治疗以及判断预后提供一个新的研究线索。     

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial

BackgroundThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir–ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.MethodIn this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.ResultsA total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.Conclusions and relevancerSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.

Key messages

• There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.
• In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir–ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.

     

Autoantibodies to epithelial cells in patients on long-term therapy with leucocyte-derived interferon-alpha (IFN-alpha).

During routine screening for anti-nuclear antibodies, using rat liver tissue as substrate, a reactivity against bile duct epithelium was observed in sera from carcinoid tumour patients given human leucocyte-derived IFN-alpha (HuLe IFN-alpha). In a retrospective study, initiated by this observation, the development of serum antibodies to bile duct epithelium was observed in nine out of 12 patients with carcinoid tumours and in three out of 14 patients with hairy-cell leukaemia during their treatment with HuLe IFN-alpha. However, no bile duct reactivity was observed in sera from carcinoid or hairy-cell leukaemia in patients given recombinant IFN-alpha. When analysing the reactivity of positive sera against a panel of rat and human tissues, a uniform reactivity was observed against simple epithelial cells lining the gastrointestinal tract, pancreatic secretory ducts, fallopian tube, kidney tubuli, mesothelium and also against carcinoid tumour cells. The mechanisms promoting autoreactivity against this simple epithelial cell autoantigen is so far unknown. The cytoplasmic as well as the restricted staining pattern of simple epithelial cells may indicate autoreactivity against certain cytoskeletal intermediate filaments, such as cytokeratin 19, 18 and 8, known to be exclusively present in simple epithelial cells and tumours derived from them.