Immunosuppression after Cardiopulmonary Bypass- Underlying Mechanisms and Strategies for Prevention

• Applicant: Professorin Dr. Simone Kreth
• Subject Area: Anaesthesiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 447514737

After cardiac surgery using the heart-lung machine, a systemic inflammatory response syndrome (SIRS) occurs, characterized by an initially strong, non-specific activation of the immune system. Simultaneously, a frequently longer lasting compensatory anti-inflammatory response syndrome is initiated. CARS is characterized by strong immunosuppression and is an important risk factor for postoperative complications such as infections and wound healing disorders. The pathophysiology of CARS is poorly understood and there are currently no reliable predictive markers or efficient therapeutic strategies.We have recently shown that particularly T-cells of patients after cardiopulmonary bypass exhibit a pronounced immunoparalytic phenotype. A transient cell population was detected and could be classified as Myeloid-derived Suppressor Cells (MDSC) by immunophenotyping. The arginase-mediated depletion of the amino acid arginine, which is essential for T cells, was identified as part of the MDSC-specific mechanisms of postoperative T cell immunosuppression. The molecular mechanisms of this immunosuppression are not yet known. In this project the underlying mechanisms of post-CBP immunosuppression will be elucidated and strategies for prevention and attenuation will be developed. Here, the focus will be on three goals:1.: Investigation of the impact of ROS on T cell immunocompetence and metabolism after CPB.2.: Identification of genes and pathways responsible for MDSC-specific immunosuppression.3.: Analysis of the impact of ROS scavenging and Arginine supplementation on CPB-induced immunosuppressionThe proposed project is intended to provide a sound basis for subsequent clinical studies on the prevention and treatment of CBP immunosuppression.

• DFG Programme: Research Grants