Lymphocytes TregFoxP3 as an Immunological Response Associated with Secondary Inflammation by Cardiopulmonary Bypass in Cardiac Surgery

Document Type : Original Article

Authors

1 Cardiovascular Surgery Department, CMN 20 de Noviembre, ISSSTE , México City.

2 Histocompatibility Laboratory, CMN 20 de Noviembre, ISSSTE, México City.

Abstract

Introduction: Cardiopulmonary Bypass (CPB) triggers a robust systemic inflammatory response, marked by elevated serum levels of inflammatory interleukins, which negatively affect endothelial function and target organs. In response to this inflammatory insult, the body activates TregFoxP3 lymphocytes, which regulate inflammation by inhibiting pro-inflammatory interleukins and promoting restorative macrophage activity. Despite this regulatory mechanism, CPB-related inflammation in cardiac surgery is often associated with hemodynamic disturbances. The impact of TregFoxP3 cell levels—whether increased or depleted—on this relationship remains unclear and was therefore evaluated.
Method: This study aimed to assess the effect of CPB on the relationship between TregFoxP3 cells and inflammatory interleukins in patients undergoing cardiac surgery. Blood samples were collected before and after the CPB procedure to measure levels of IL-2, IL-6, IL-8, and TNF-α using chemiluminescence, and TregFoxP3 lymphocytes were quantified via flow cytometry.
Results: A total of 32 patients (mean age 65 ± 5 years), primarily undergoing cardiac valve replacement (80%), were included in the analysis. The average CPB duration was 80 ± 20 minutes, with aortic clamping lasting 60 ± 15 minutes. Following CPB, serum levels of IL-6, IL-8, TNF-α, and TregFoxP3 significantly increased, while IL-2 levels significantly decreased (p = 0.001). Baseline TregFoxP3 levels showed no correlation with inflammatory interleukins; however, post-CPB levels demonstrated a strong and significant positive correlation (r > 0.50, p = 0.001), except for IL-2, which showed a negative association.
Conclusion: The TregFoxP3 lymphocyte response is strongly and significantly correlated with inflammatory interleukin levels following cardiac surgery involving Cardiopulmonary Bypass, highlighting its potential role in modulating postoperative inflammation.

Keywords

References

  1. Mensah GA, Fuster V, Murray CJ, Roth GA, Global Burden of Cardiovascular Diseases and Risks Collaborators. Global burden of cardiovascular diseases and risks, 1990-2022. Journal of the American College of Cardiology. 2023 Dec 19;82(25):2350-473.
  2. Menotti A, Puddu PE. In Search of Risk Factors: The Origin and Early Stages of Cardiovascular Epidemiology. Journal of Cardiovascular Development and Disease. 2024 Jan 12;11(1):20.
  3. Bronicki RA, Hall M. Cardiopulmonary bypass-induced inflammatory response: pathophysiology and treatment. Pediatric Critical Care Medicine. 2016 Aug 1;17(8):S272-8.
  4. Punjabi PP, Taylor KM. The science and practice of cardiopulmonary bypass: From cross circulation to ECMO and SIRS. Global cardiology science & practice. 2013 Nov 1;2013(3):249.
  5. Rodríguez-Morales M, Díaz-Quiroz G, Aceves-Chimal JL, Flores-Calderón O, García-Ortegón MS, Jaime-Uribe A, et al. Regulatory T cells in the inflammatory balance as a response to extracorporeal circulation in cardiac surgery. A narrative review. Cirugía Cardiaca en México. 2024 Feb 21;9(1):10-29.
  6. Alvarez F, Al-Aubodah TA, Yang YH, Piccirillo CA. Mechanisms of TREG cell adaptation to inflammation. Journal of Leucocyte Biology. 2020 Aug;108(2):559-71.
  7. Hobbs FR, Hoes AW, Cowie MR. The epidemiology of cardiovascular disease. Cardiovascular risk management. 2008 Nov 28:1-7.
  8. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert review of cardiovascular therapy. 2013 Jan 1;11(1):55-9.
  9. Ethier JL, Desautels D, Templeton A, Shah PS, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Research. 2017 Jan 5;19(1):2.
  10. Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P, Lim E. Neutrophil/lymphocyte ratio and its association with survival after complete resection in non–small cell lung cancer. The Journal of thoracic and cardiovascular surgery. 2009 Feb 1;137(2):425-8.
  11. Kawahara T, Kato M, Tabata K, Kojima I, Yamada H, Kamihira O, et al. A high neutrophil-to-lymphocyte ratio is a poor prognostic factor for castration-resistant prostate cancer patients who undergo abiraterone acetate or enzalutamide treatment. BMC cancer. 2020 Sep 25;20(1):919.
  12. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010 Mar 4;464(7285):104-7.
  13. Margraf A, Ludwig N, Zarbock A, Rossaint J. Systemic inflammatory response syndrome after surgery: mechanisms and protection. Anesthesia & Analgesia. 2020 Dec 1;131(6):1693-707.
  14. Jarczak D, Nierhaus A. Cytokine storm—definition, causes, and implications. International journal of molecular sciences. 2022 Oct 3;23(19):11740.
  15. Marik PE, Flemmer M. The immune response to surgery and trauma: implications for treatment. Journal of Trauma and Acute Care Surgery. 2012 Oct 1;73(4):801-8.
Journal of Cardio-Thoracic Medicine
Volume 13, Issue 4
December 2025
Pages 1604-1607

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