Sevoflurane modulates the release of reactive oxygen species, myeloperoxidase, and elastase in human whole blood: Effects of different stimuli on neutrophil response to volatile anesthetic in vitro

Abstract

Volatile anesthetics have been shown to modulate polymorphonuclear neutrophil (PMN) functions. The aim of this study was to examine the impact of clinically relevant concentrations of sevoflurane (SEVO), a volatile anesthetic, on the release of reactive oxygen species (ROS), myeloperoxidase (MPO), and elastase (EL) from human activated PMNs. For this purpose, samples of whole blood were collected from healthy volunteers and exposed in vitro to 2.3% or 4.6% SEVO in air. To assess for a stimulus-dependent effect of the volatile anesthetic, PMNs were activated using different validated protocols. Artificial stimulation of neutrophils involved either a combination of cytochalasin B (CB) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). In addition, a combination of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α) was also tested as a natural activation mean of PMNs. The production of ROS by PMNs was assessed by L-012 chemiluminescence. Total MPO and EL released in supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, degranulation of the active fraction of MPO was also measured by specific immunological extraction followed by enzymatic detection (SIEFED). Overall, SEVO enhanced the release of ROS, MPO, and EL following artificial stimulation of PMNs but the volatile anesthetic inhibited the degranulation of active MPO and EL after neutrophil exposure to LPS and TNF-α. This study highlighted that the effect of SEVO on activated PMNs is dependent on the conditions of cell stimulation. These properties should be taken into consideration in future studies investigating immunomodulatory effects of volatile anesthetics.

A preliminary study to assess neutrophil and endothelial response to knee arthroplasty with the use of a tourniquet : effects of spinal or sevoflurane anesthesia

“…Differentiation of active MPO from total MPO is clinically relevant for two reasons. First, active MPO is a more sensitive marker of neutrophil degranulation than total MPO (15). The better sensitivity of the SIEFED assay over the ELISA is further confirmed in the present work where active but not total MPO increased after tourniquet deflation.…”

Comparison between sevoflurane and propofol on immunomodulation in an in vitro model of sepsis

“…In a previous endotoxemia model, sevoflurane enhanced macrophage phagocytosis in vitro through an inducible nitric oxide synthase (iNOS)-dependent mechanism ( 18 ). During sepsis, pro-inflammatory cytokines such as TNF-α and IL-1β are released by sentinel innate immune cells at the infection site and activated by pathogen-associated molecular pattern (PAMPS) and damage-associated molecular pattern (DAMPS) ( 40 ). These cytokines activate neutrophils, lead to increased expression of β-integrins on the cell surface of neutrophils, and interact with highly expressed adhesion molecules on the vascular endothelium and neutrophils leave the vasculature based on chemoattractant gradient ( 41 ).…”

Possibilities of inhalation anesthetics in blocking an excessive inflammatory response: a review

“…В исследованиях in vitro окислительный стресс (выработка АФК) снижался под воздействием севофлу рана и изофлурана в экспериментальных моделях сепсиса, острого респираторного дистресс-синдрома (ОРДС), воспаления [28][29][30][31][32]. В других исследованиях было выявлено, что образование АФК и хемотаксис снижались после воздействия севофлураном, десфлураном, галотаном и энфлураном.…”