Effect Of Cytokines In Host Defense And Inflammation

点击翻译按钮获取中文摘要

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.