Simvastatin inhibits the inflammation and oxidative stress of human neutrophils in sepsis via autophagy induction.

Abstract

Simvastatin exerts a protective effect during sepsis (SP) in animal models; however, the underlying mechanism is not completely understood, particularly in human SP. Neutrophils are a critical effector in the host inflammatory response to SP. Therefore, the present study aimed to investigate the effect of simvastatin on neutrophils in human SP. Neutrophils were isolated from the peripheral venous blood of adult patients with SP and healthy volunteers (HP). Cell viability was analyzed using the MTT assay. Intracellular reactive oxygen species (ROS) generation and the concentrations of inflammatory mediators were also assessed using flow cytometry and ELISA. The results demonstrated that the cell viability of neutrophils from the SP group was significantly decreased compared with that in the HP group, and that treatment with simvastatin partly reversed the reduced cell viability. Furthermore, simvastatin administration significantly decreased ROS production and the concentrations of TNF‑α and IL‑6, which were significantly increased in neutrophils isolated from the SP group. Simvastatin also enhanced autophagy induction, as indicated by the promotion of the conversion of LC3I to LC3II and the increased expression levels of Beclin 1 in SP neutrophils. Treatment with 3‑methyladenine, an autophagy inhibitor, completely blocked the protective effects of simvastatin on neutrophils from SP, including the effects of simvastatin on the inhibition of inflammation, oxidative stress and improving cell viability. Collectively, the present study provided evidence for the simvastatin‑induced autophagic process of neutrophils involved in human SP, which protects neutrophils and partially attenuates the inflammatory response and oxidative stress. Therefore, the augmentation of neutrophil autophagy may serve as a potential therapeutic target for patients with SP.

• Authors: Li Xu, Xiao-Min Wu, Yu-Kun Zhang, Ming-Jie Huang, Jun Chen
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 25 Issue 1 (01 2022) ISSN: 1791-3004 [Electronic] Greece
• PMID: 34812477 (Publication Type: Journal Article)

Chemical References

• Beclin-1
• Cytokines
• Inflammation Mediators
• Interleukin-6
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Simvastatin

Topics

• Adult
• Aged
• Animals
• Autophagy (drug effects)
• Beclin-1 (metabolism)
• Cell Survival (drug effects)
• Cytokines (metabolism)
• Female
• Humans
• Inflammation (drug therapy)
• Inflammation Mediators (metabolism)
• Interleukin-6 (metabolism)
• Male
• Middle Aged
• Neutrophils (metabolism)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Sepsis (metabolism)
• Simvastatin (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)