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)水泡法正被用于评估几种罕见免疫缺陷患者的体内炎症反应，包括STAT3缺陷、CGD等。我们对STAT3缺乏症的一些研究结果已经提交发表。利用正常受试者，我们与Doug Kuhns(SAIC)合作，检测人类炎性白细胞作为T细胞功能的髓系抑制细胞的能力。 2)在2012财年，我们继续招募患者参加NIH议定书#10-I-0123《慢性肉芽肿性疾病特定基因突变受试者对干扰素-伽马的生化反应评估》。这项研究将测试潜在突变和/或残留NADPH氧化酶活性不同的CGD患者亚群是否更有可能从干扰素-伽玛治疗中受益。干扰素-γ已在临床上用于CGD患者，以降低感染率。然而，这种昂贵药物作用的机制和CGD患者之间临床反应的广泛差异都不清楚。我们的假设是，只有特定的CGD患者亚组，特别是那些ROS水平较高的患者可能对干扰素治疗有效并受益于干扰素治疗。这项研究的完成可能会显著节省成本，并减少与干扰素治疗相关的发病率。