Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5). Our results showed that VAs, not an intravenous anesthetic, significantly attenuated the activation of TLR5 and the release of the neutrophil chemoattractant IL-8 from lung epithelial cells. Furthermore, flagellin-induced lung injury was significantly attenuated by VAs by inhibiting neutrophil migration to the bronchoalveolar space. The lungs of cystic fibrosis (CF) patients are highly colonized by Pseudomonas aeruginosa, which causes inflammation. The retrospective study of oxygenation in patients with CF who had received VA versus intravenous anesthesia suggested that VAs might have the protective effect for gas exchange. To understand the interaction between VAs and TLR5, a docking simulation was performed, which indicated that isoflurane and sevoflurane docked into the binding interphase between TLR5 and flagellin. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Isoflurane and sevoflurane, commonly used volatile anesthetics, show immunomodulatory effects and may impact disease progression by attenuating lung injury and inhibiting TLR5 activation. Studies suggest they have a protective effect on gas exchange in patients with cystic fibrosis. Additionally, docking simulations indicate these anesthetics interact with TLR5 and flagellin for potential therapeutic benefits.