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: 8745306
• 负责人: JOHN I GALLIN
• 金额: $ 11.37万
• 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/8745306
• 关键词: Acute; Biochemical; Bulla; Cell physiology; Chronic Granulomatous Disease; Clinical; Clinical Research; Cost Savings; Defect; Development; Drug effect disorder; Enrollment; Gene Mutation; Genetic; Goals; Host Defense; Human; Immune System Diseases; Immunologic Deficiency Syndromes; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Interferon Type II; Interferons; Leukocytes; Modeling; Morbidity - disease rate; Mutation; Myelogenous; NADPH Oxidase; Patients; Production; Protocols documentation; Residual state; STAT3 gene; Skin; Sterility; Subgroup; Superoxides; Suppressor-Effector T-Lymphocytes; T-Lymphocyte; Testing; United States National Institutes of Health; Variant; cytokine; in vitro Assay; in vivo; killings; monocyte; 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. 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. We continue to accrue subjects with CGD in order to examine the development and progression of inflammation in vivo in this patient population. 2) During FY13, 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 (2 subjects completed study by end of FY13). 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. Relevant to this clinical study, are in vitro studies by Chu et al. (see ZIA AI001151-03) that demonstrate a positive correlation between residual PMN superoxide production and the ability of monocytes to kill G.bethesdensis following IFNgamma treatment. This finding provides an in vitro assay to predict which patients may respond in vivo to IFNgamma.

1)水疱方案被用于评估几个罕见免疫缺陷患者群体的体内炎症，包括STAT 3缺陷、CGD等。 使用正常受试者，我们正在与Doug Kuhns（SAIC）合作，以检查人类炎性白细胞作为T细胞功能的髓系抑制细胞的能力。 我们继续招募CGD受试者，以检查该患者人群体内炎症的发生和进展。 2)在2013财年期间，我们继续招募患者参加NIH方案#10-I-0123慢性肉芽肿性疾病特定基因突变受试者对IFN-γ的生化反应评估（2例受试者在2013财年结束时完成研究）。 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。 与该临床研究相关的是Chu等人的体外研究（参见ZIA AI 001151 -03），其证明了IFN γ处理后残留PMN超氧化物产生与单核细胞杀死贝塞登革菌的能力之间的正相关性。 这一发现提供了一种体外试验，以预测哪些患者可能在体内对IFN γ产生反应。