Xiao-Yang Zhang1,2, Lin Zhou3, Zhen Guo4, Ye Kong5, Wei Zhang5, Li-Ming Lu6, Xin Li7. 1. Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Heart Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200120, China. 2. Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China. 3. Research Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China. 4. Department of Extracorporeal Circulation, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China. 5. Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China. 6. Shanghai Institute of Immunology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200020, China. 7. Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Abstract
BACKGROUND: Postoperative pulmonary dysfunction (PPD) is a common complication observed in patients after cardiac surgery with cardiopulmonary bypass (CPB). The underlying mechanism regulating lung injury after CPB is unclear. However, since the involvement of regulatory T (Treg) cells and T helper 17 (Th17) cells in immune responses has been well established, in this study, we investigated the contribution of these lymphocyte subsets to the development of PPD after CPB. METHODS: Fifty-six rheumatic heart disease (RHD) patients' blood samples were collected at different time points before and after surgery. The samples were analyzed by flow cytometry to quantify cells and by enzyme-linked immunosorbent assay (ELISA) to measure the cytokine content. In addition, the inhibitory function of Treg cells of ten patients was tested before and after surgery. RESULTS: We showed that a decreased percentage of Treg cells and reduced Treg/Th17 ratio before anesthesia and after neutralization are meaningful predictors of severe PPD (AUC 0.722, 95% CI: 0.557 to 0.888; 0.787, 95% CI: 0.639 to 0.934; 0.751, 95% CI: 0.593 to 0.919; 0.551, 95% CI: 0.366 to 0.735). Interestingly, both the percentage of Treg cells and their suppressive effect on effector T lymphocyte (Teff) cells were increased after CPB, and both effects may play a protective role in PPD. By contrast, severe PPD was associated with increased IL-17A levels. CONCLUSIONS: The increased proportion of Treg cells in the CD4+ T cell population and higher ratio of Treg/Th17 before anesthesia induction and 30 min after heparin neutralization can partially protect patients from a severe inflammatory response and PPD.
BACKGROUND: Postoperative pulmonary dysfunction (PPD) is a common complication observed in patients after cardiac surgery with cardiopulmonary bypass (CPB). The underlying mechanism regulating lung injury after CPB is unclear. However, since the involvement of regulatory T (Treg) cells and T helper 17 (Th17) cells in immune responses has been well established, in this study, we investigated the contribution of these lymphocyte subsets to the development of PPD after CPB. METHODS: Fifty-six rheumatic heart disease (RHD) patients' blood samples were collected at different time points before and after surgery. The samples were analyzed by flow cytometry to quantify cells and by enzyme-linked immunosorbent assay (ELISA) to measure the cytokine content. In addition, the inhibitory function of Treg cells of ten patients was tested before and after surgery. RESULTS: We showed that a decreased percentage of Treg cells and reduced Treg/Th17 ratio before anesthesia and after neutralization are meaningful predictors of severe PPD (AUC 0.722, 95% CI: 0.557 to 0.888; 0.787, 95% CI: 0.639 to 0.934; 0.751, 95% CI: 0.593 to 0.919; 0.551, 95% CI: 0.366 to 0.735). Interestingly, both the percentage of Treg cells and their suppressive effect on effector T lymphocyte (Teff) cells were increased after CPB, and both effects may play a protective role in PPD. By contrast, severe PPD was associated with increased IL-17A levels. CONCLUSIONS: The increased proportion of Treg cells in the CD4+ T cell population and higher ratio of Treg/Th17 before anesthesia induction and 30 min after heparin neutralization can partially protect patients from a severe inflammatory response and PPD.
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