Reactive oxygen species elevations in human immune cell subsets during sepsis are mitigated by norepinephrine and N-acetylcysteine
Year: 2025
Type: article
Abstract: BACKGROUND Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Peripheral blood mononuclear cells (PBMCs) are critical mediators of the immune response and may exhibit redox imbalance during sepsis. Reactive oxygen species (ROS) are known to influence immune cell signaling, and excessive ROS accumulation may contribute to sepsis-associated immune alterations. AIM To assess intracellular ROS levels in PBMC subsets from septic patients and determine whether norepinephrine (NE) or N-acetylcysteine (NAC) modulate ROS levels following inflammatory stimulation in vitro . METHODS PBMCs were isolated from Department of Emergency patients meeting SEP-1/SEP-2 sepsis criteria and from healthy controls without signs of infection. Intracellular ROS levels were measured using a total ROS detection assay and analyzed by flow cytometry. PBMCs were also stimulated in vitro with lipopolysaccharide (LPS) or hydrogen peroxide (H2O2), with or without co-treatment with NE or NAC. RESULTS ROS levels were significantly elevated in CD3+ and CD14+ cells from septic patients compared to controls. In vitro stimulation of control PBMCs with LPS or H2O2 increased ROS in CD3+ and CD14+ cells, which was attenuated by co-treatment with NE or NAC. CONCLUSION ROS levels are elevated in specific PBMC subsets in sepsis, particularly CD3+ T cells and CD14+ monocytes. NE and NAC reduced ROS accumulation in vitro , supporting their potential role as redox modulators. These findings warrant further mechanistic investigation into immune redox regulation in sepsis.
Authors: Joby Thoppil, J David Farrar, Drashya Sharma, Shaun Kirby, Angela Mobley, Daniel Mark Courtney
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4416757734