Effect Of Cytokines In Host Defense And Inflammation

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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.