Urinary Trypsin Inhibitor Attenuated Inflammatory Response of Patients Undergoing Cardiopulmonary Bypass by Inducing Act
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Urinary Trypsin Inhibitor Attenuated Inflammatory Response of Patients Undergoing Cardiopulmonary Bypass by Inducing Activated Treg Cells Xing Hao,1 Junyan Han,2,3 Zhichen Xing,1 Yu Hao,2,3 Chunjing Jiang,1 Jianping Zhang,2,3 Jing Yang,1 and Xiaotong Hou1,4
ABSTRACT—The urinary trypsin inhibitor (ulinastatin) is used in the clinic to prevent inflammatory responses in patients undergoing cardiopulmonary bypass (CPB); however, the anti-inflammatory mechanism is unclear. In the current study, we recruited 40 patients undergoing selective cardiac valve replacement surgery; and these patients were randomly divided into two groups (ulinastatin group [UG] and control group [CG]). We collected peripheral blood preoperatively, at the end of CPB, and postoperative days 1 and 3 and analyzed the kinetic changes in regulatory T (Treg) cell subsets. There was no statistically significant difference in the number of CD4+ T cells between the two groups. The number of CD4+CD25+ Treg cells, especially the suppressive activated Treg (aTreg) subset, was higher in the UG than the CG 1 and 3 days postoperatively. Thus, ulinastatin alleviated the inflammatory response during CPB by inducing the expansion of aTreg cells. KEY WORDS: cardiopulmonary bypass; inflammation responses; ulinastatin; regulatory T cells.
INTRODUCTION Cardiopulmonary bypass (CPB) has been widely used to maintain systemic perfusion and oxygenation during open heart surgery; however, CPB can induce severe systemic inflammatory response syndrome (SIRS) during open heart surgery. “Contact activation” between blood and non-biocompatible membranes leads to leucopenia. The patients who develop SIRS are susceptible to infection,
Xing Hao and Junyan Han contributed equally to this work. 1
Department of Extracorporeal Circulation, Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anding Road, Chaoyang District, Beijing, 100029, China 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China 3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China 4 To whom correspondence should be addressed at Department of Extracorporeal Circulation, Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anding Road, Chaoyang District, Beijing, 100029, China. E-mail: [email protected] ABBREVIATIONS: CPB, Cardiopulmonary bypass; TNF-α, Tumor necrosis factor-alpha; IL, Interleukin; AAo, Ascending aorta; CRP, Creactive protein
which could cause significant morbidity and mortality. The urinary trypsin inhibitor (UTI, ulinastatin) has been used widely in the clinic for preventing inflammatory responses in patients undergoing CPB. Several mechanisms possibly contribute to the anti-inflammatory effect of UTI. Previous studies involving the anti-inflammatory mechanism of UTI have mainly focused on the roles of cytokines [1–4]. UTI treatment markedly attenuates LPS-induced acute lung injury, probably by adjusting the balance between proinflammatory an
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