The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis.

Autor: Coman O; Department of Simulation Applied in Medicine, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania., Grigorescu BL; Department of Anaesthesiology and Intensive Therapy, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania., Huțanu A; Department of Laboratory Medicine, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania.; Center for Advanced Medical and Pharmaceutical Research, Immunology, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania., Bacârea A; Department of Pathophysiology, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania., Văsieșiu AM; Department of Infectious Disease, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania., Fodor RȘ; Department of Anaesthesiology and Intensive Therapy, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania., Stoica F; Clinic of Internal Medicine II, Emergency County Hospital, 540136 Targu Mures, Romania., Azamfirei L; Department of Anaesthesiology and Intensive Therapy, University of Medicine, Pharmacy, Science and Technology 'George Emil Palade', 540142 Targu Mures, Romania.
Jazyk: angličtina
Zdroj: Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2024 Jul 19; Vol. 60 (7). Date of Electronic Publication: 2024 Jul 19.
DOI: 10.3390/medicina60071174
Abstrakt: Background and Objectives : Sepsis involves a dysregulated host response, characterized by simultaneous immunosuppression and hyperinflammation. Initially, there is the release of pro-inflammatory factors and immune system dysfunction, followed by persistent immune paralysis leading to apoptosis. This study investigates sepsis-induced apoptosis and its pathways, by assessing changes in PD-1 and PD-L1 serum levels, CD4+ and CD8+ T cells, and Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) severity scores. Materials and Methods : This prospective, observational, single-centre study enrolled 87 sepsis patients admitted to the intensive care unit at the County Emergency Clinical Hospital in Târgu Mureș, Romania. We monitored the parameters on day 1 (the day sepsis or septic shock was diagnosed as per the Sepsis-3 Consensus) and day 5. Results : Our study found a statistically significant variation in the SOFA score for the entirety of the patients between the studied days ( p = 0.001), as well as for the studied patient groups: sepsis, septic shock, survivors, and non-survivors ( p = 0.001, p = 0.003, p = 0.01, p = 0.03). On day 1, we found statistically significant correlations between CD8+ cells and PD-1 ( p = 0.02) and PD-L1 ( p = 0.04), CD4+ and CD8+ cells ( p < 0.0001), SOFA and APACHE II scores ( p < 0.0001), and SOFA and APACHE II scores and PD-L1 ( p = 0.001 and p = 0.01). On day 5, we found statistically significant correlations between CD4+ and CD8+ cells and PD-L1 ( p = 0.03 and p = 0.0099), CD4+ and CD8+ cells ( p < 0.0001), and SOFA and APACHE II scores ( p < 0.0001). Conclusions : The reduction in Th CD4+ and Tc CD8+ lymphocyte subpopulations were evident from day 1, indicating that apoptosis is a crucial factor in the progression of sepsis and septic shock. The increased expression of the PD-1/PD-L1 axis impairs costimulatory signalling, leading to diminished T cell responses and lymphopenia, thereby increasing the susceptibility to nosocomial infections.
Databáze: MEDLINE