stat3 regulates monocyte tnf-alpha production in systemic inflammation caused by cardiac surgery with cardiopulmonary bypassstat3调节单核细胞tnf在系统性炎症引起的生产与体外循环心脏手术.pdfVIP

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass 1,2. 1,2. 1,2 3 Petrus R. de Jong , Alvin W. L. Schadenberg , Theo van den Broek , Jeffrey M. Beekman , 2 2,3 2. 1 . Femke van Wijk , Paul J. Coffer , Berent J. Prakken , Nicolaas J. G. Jansen * 1 Department of Pediatric Intensive Care, University Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, The Netherlands, 2 Deptartment of Pediatric Immunology, Center for Molecular and Cellular Intervention, University Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, The Netherlands, 3 Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands Abstract Background: Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-a production by monocytes. Methodology/Principal Findings: Pediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n = 38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes ob