title: The volatile anaesthetic sevoflurane attenuates lipopolysaccharide-induced injury in alveolar macrophages.
abstract: Acute lung injury (ALI) is a well-defined inflammation whereby alveolar macrophages play a crucial role as effector cells. As shown previously in numerous experimental approaches, volatile anaesthetics might reduce the degree of injury in pre- or post-conditioning set-ups. Therefore, we were interested to evaluate the effect of the application of the volatile anaesthetic sevoflurane on alveolar macrophages regarding the expression of inflammatory mediators upon lipopolysaccharide (LPS) stimulation in vitro. Alveolar macrophages were stimulated with LPS. Two hours later, cells were exposed additionally to air (control) or to sevoflurane-containing air for 4, 6, 8, 12 or 24 h. Tumour necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage-inflammatory protein-2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1) proteins were determined and chemotaxis assays were performed. To evaluate possible cellular signalling pathways phosphorylation of the kinases extracellular-regulated kinase (ERK) and Akt was assessed. In the early phase of sevoflurane post-conditioning expression of TNF-alpha, CINC-1, MIP-2 and MCP-1 was attenuated, leading to a diminished chemotaxis reaction for neutrophils. Phosphorylation of ERK seems to be a possible cellular mechanism in the sevoflurane-induced protection in vitro. Pharmacological post-conditioning of alveolar macrophages with sevoflurane immunmodulates the inflammatory response upon stimulation with endotoxin. This might be a possible option for a therapeutical approach in ALI.
authors.affiliation: Institute of Physiology, Zurich Center of Integrative Human Physiology, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Steurer
authors.forename: M
authors.initials: M
authors.lastname: Schläpfer
authors.forename: M
authors.initials: M
authors.lastname: Steurer
authors.forename: B Roth
authors.initials: BR
authors.lastname: Z'graggen
authors.forename: C
authors.initials: C
authors.lastname: Booy
authors.forename: L
authors.initials: L
authors.lastname: Reyes
authors.forename: D R
authors.initials: DR
authors.lastname: Spahn
authors.forename: B
authors.initials: B
authors.lastname: Beck-Schimmer
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000473:pathology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D051381:Rats; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D008738:Methyl Ethers; D014409:Tumor Necrosis Factor-alpha; D000077149:Sevoflurane