Postconditioning with a volatile anaesthetic in alveolar epithelial cells in vitro

Abstract

Acute lung injury is a common complication in critically ill patients. The present study examined possible immunomodulating effects of the volatile anaesthetic sevoflurane on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (AEC) in vitro.Sevoflurane was applied after the onset of injury, simulating a ''postconditioning'' scenario. Rat AEC were stimulated with LPS for 2 h, followed by a 4-h co-exposure to a CO 2 /air mixture with sevoflurane 2.2 volume %; control cells were exposed to the CO 2 /air mixture only. Cytokineinduced neutrophil chemoattractant-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, as well as the potential protective mediators inducible nitric oxide synthase (iNOS)2 and heat shock protein (HSP)-32, were analysed. Additionally, functional assays (chemotaxis, adherence and cytotoxicity assay) were performed.A significant reduction of inflammatory mediators in LPS-stimulated, sevoflurane-exposed AEC was found, leading to reduced chemotaxis, neutrophil adherence and neutrophil-induced AEC killing. While iNOS2 was increased in the sevoflurane group, blocking experiments with iNOS2 inhibitor did not affect sevoflurane-induced decrease of inflammatory mediators and AEC killing. Interestingly, sevoflurane treatment also resulted in an enhanced expression of HSP-32.The data presented in the current study provide strong evidence that anaesthetic postconditioning with sevoflurane mediates cytoprotection in the respiratory compartment in an in vitro model of acute lung injury.

The Anti-Inflammatory and Immunosuppressive Properties of Inhaled Anaesthetics - Data from Experimental Studies and Clinical Implications

“…Attenuated expression of inflammatory mediators described by Urner et al, observed during conditioning with sevoflurane is consistent with the results of previously described studies, while increased expression of MCP-1 was typical of diethyl ether (50). This suggested that diethyl ether had proinflammatory effect, while fluorinated carbon groups were essential for the cytoprotective effect of volatile anaesthetics.…”

Sevoflurane improves gaseous exchange and exerts protective effects in lipopolysaccharide-induced lung injury in mice models

“…Sevoflurane is one of the commonly used sedatives and acts as pre-conditioning as well as post-conditioning agent by protecting organs in ALI models through inhibition of pro-inflammatory expressions [10]. In the present study, the effects of sevoflurane on gaseous exchange, antioxidant defense system and LPS-induced lung tissue injuries were investigated in a mice model of ALI.…”

“…Volatile anesthetics have also been reported to exhibit anti-inflammatory activities [6][7][8][9]. Sevoflurane, which is one of the commonly used sedatives acts as pre-conditioning as well as postconditioning agent [10] by the protecting organs in ALI models through inhibition of proinflammatory expressions. Moreover, ALI leads to increased accretion of ROS and myeloperoxidase (MPO), and reduces the levels of ROS scavengers such as GSH and superoxide dismutase (SOD), which confer protection against oxidative damage in vivo [11].…”

The volatile anesthetic sevoflurane attenuates ventilatorinduced lung injury through inhibition of ERK1/2 and Akt signal transduction

“…Lee et al [25] reported that volatile anesthetics had anti-inflammatory properties, and the maximal effect on sevoflurane ischemic protection was achieved with 1.1 vol% in the kidney proximal tubule. A study on alveolar epithelial cells reported that a reduction of inflammatory mediators was achieved when the inflammatory mediators were stimulated by LPS for 2 h, followed by exposure to a 2.2 vol% sevoflurane concentration for 4 h [26]. In a study on the postconditioning effects of various concentrations of volatile anesthetic sevoflurane used on inflammatory mediator expression via LPS stimulation in alveolar macrophages, inflammatory mediator expression was significantly reduced with a 3.3 vol% concentration of sevoflu-VOL.…”