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: 8555770
• 负责人: JOHN I GALLIN
• 金额: $ 11.32万
• 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/8555770
• 关键词: Acute; Biochemical; Bulla; Cell physiology; Chronic Granulomatous Disease; Clinical; Clinical Trials; Cost Savings; Defect; Drug effect disorder; Enrollment; Gene Mutation; Genetic; Goals; Host Defense; Human; Immune System Diseases; Immunologic Deficiency Syndromes; Infection; Inflammation; Inflammatory; Inflammatory Response; Interferon Type II; Interferons; Leukocytes; Modeling; Morbidity - disease rate; Mutation; Myelogenous; NADPH Oxidase; Patients; Protocols documentation; Publications; Residual state; STAT3 gene; Skin; Sterility; Subgroup; Suppressor-Effector T-Lymphocytes; T-Lymphocyte; Testing; United States National Institutes of Health; Variant; cytokine; in vivo; patient population; response

1) The blister protocol is being used to evaluate inflammation in vivo in several populations of patients with rare immunodeficiencies including STAT3 deficiency, CGD, and others. Results from some of our studies of STAT3 deficiency have been submitted for publication. Using normal subjects, we are collaborating with Doug Kuhns (SAIC), to examine the ability of human inflammatory leukocytes to act as myeloid suppressor cells of T-cell function. 2) During FY12, we have continued to enroll 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）水泡方案用于评估几个罕见免疫缺陷患者的体内炎症，包括STAT3缺乏症，CGD等。 我们对STAT3缺乏症的一些研究的结果已提交出版。 使用正常受试者，我们正在与道格·库恩（Doug Kuhns）（SAIC）合作，以检查人类炎性白细胞充当T细胞功能的髓样抑制细胞的能力。 2）在2012财年期间，我们继续将患者纳入NIH方案＃10-I-0123评估对慢性肉芽肿性疾病中特定基因突变受试者的生化反应对IFN-GAMMA的生化反应。 这项研究将测试CGD患者的亚群，即潜在的突变和/或残留的NADPH氧化酶活性不同，更可能从IFN-GAMMA治疗中受益。干扰素伽马已在CGD患者的临床上用于降低感染率。但是，这种昂贵的药物作用的机制和CGD患者临床反应的广泛差异均不知道。我们的假设是，只有某些CGD患者的某些亚组，特别是那些可检测到较高水平的ROS的患者可能会对干扰素治疗有反应并受益。这项研究的完成可能会导致大量的成本节省，并降低与干扰素治疗相关的发病率。