Reactive oxygen species elevations in human immune cell subsets during sepsis are mitigated by norepinephrine and N-acetylcysteine

脓毒症期间,人体免疫细胞亚群中活性氧的升高可通过去甲肾上腺素和N-乙酰半胱氨酸得到缓解。

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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 (H(2)O(2)), 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 H(2)O(2) 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.

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