Effect Of Cytokines In Host Defense And Inflammation

细胞因子在宿主防御和炎症中的作用

• 批准号: 8336064
• 负责人: JOHN I GALLIN
• 金额: $ 19.01万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336064
• 关键词: Acute; Biochemical; Bulla; Cell physiology; Cells; Chronic Granulomatous Disease; Clinical; Clinical Trials; Collaborations; Cost Savings; Defect; Drug effect disorder; Enrollment; Gene Mutation; Genetic; Host Defense; Immune System Diseases; Immunologic Deficiency Syndromes; Infection; Inflammation; Inflammatory; Inflammatory Response; Interferon Type II; Interferons; Liquid substance; Modeling; Morbidity - disease rate; Mutation; Myelogenous; NADPH Oxidase; Patients; Play; Protocols documentation; Residual state; Role; Skin; Sterility; Subgroup; Suppressor-Effector T-Lymphocytes; Testing; United States National Institutes of Health; Variant; cytokine; immunoregulation; in vitro Assay; response; tumorigenesis

1) During FY2011, this project expanded to study the possible role of inflammatory cells and fluids in the activity of myeloid-derived suppressor cells thought to play a role in tumorigenesis and immunoregulation. In collaboration with Doug Kuhns (SAIC), we enrolled 7 normal subjects to successfully establish our in vitro assay of myeloid suppressor cell function. In the coming year, we will determine whether patients with various primary immunodeficiencies may display abnormal myeloid suppressor activity. 2) During FY11, we enrolled our first patients in NIH Protocol #10-I-0123 Assessment of the Biochemical Response to IFN-gamma in Subjects with Specific Gene Mutations in Chronic Granulomatous Disease. This study will test whether subpopulations of CGD patients, differing in underlying mutation and/or residual NADPH oxidase activity, are more likely to benefit from IFN-gamma treatment. Interferon-gamma has been used clinically in CGD patients to reduce the rates of infection. However, neither the mechanism of this costly drugs actions nor the wide variation in clinical response among CGD patients is known. Our hypothesis is that only certain subgroups of CGD patients, specifically those with higher detectable levels of ROS may be responsive to and benefit from Interferon treatment. Completion of this study may result in significant cost savings and a reduction in morbidity associated with interferon treatment.

1)在2011财政年度，该项目扩展到研究炎症细胞和液体在髓源性抑制细胞活性中的可能作用，这些细胞被认为在肿瘤发生和免疫调节中发挥作用。 与Doug Kuhns（SAIC）合作，我们招募了7名正常受试者，成功建立了骨髓抑制细胞功能的体外测定。 在未来的一年里，我们将确定是否有各种原发性免疫缺陷的患者可能会显示异常的骨髓抑制活性。 2)在2011财年，我们在NIH方案#10-I-0123评估慢性肉芽肿性疾病特定基因突变受试者对IFN-γ的生化反应中招募了首批患者。 这项研究将测试CGD患者的亚群，在潜在的突变和/或残留的NADPH氧化酶活性不同，是否更有可能从IFN-γ治疗中获益。 干扰素-γ已在临床上用于CGD患者以降低感染率。 然而，这种昂贵药物的作用机制和CGD患者临床反应的广泛差异都不清楚。我们的假设是，只有某些CGD患者亚组，特别是那些具有较高可检测水平的ROS的患者可能对干扰素治疗有反应并从中受益。 本研究的完成可能导致显著的成本节约和与干扰素治疗相关的发病率降低。