The immunomodulatory effect of sevoflurane in endotoxin-injured alveolar epithelial cells.
BACKGROUND
Endotoxin-induced lung injury is a useful experimental system for the characterization of immunopathologic mechanisms in acute lung injury. Although alveolar epithelial cells (AEC) are directly exposed to volatile anesthetics, there is limited information about the effect of anesthetics on these cells. In this study we investigated the effect of pretreatment with the inhaled anesthetic sevoflurane on lipopolysaccharide (LPS)-injured AEC.


METHODS
AEC were incubated with 1.1 vol % sevoflurane for 0.5 h, followed by LPS stimulation for 5 h. Expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1beta (MIP-1beta), macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant-1 (CINC-1), and intercellular adhesion molecule-1 (ICAM-1) was analyzed. In addition, functional tests were performed through chemotaxis and adherence assays to underline the biological relevance of the findings.


RESULTS
Exposure of AEC to sevoflurane resulted in a 50% downregulation of MCP-1 protein in the sevoflurane-LPS group when compared with non-sevoflurane- LPS cells (P < 0.05). MIP-1beta concentration in LPS-stimulated cells decreased by 32% with sevoflurane (P < 0.05), MIP-2 by 29% (P < 0.05), and CINC-1 by 20% (P < 0.05). ICAM-1 protein expression was attenuated by 36% (P < 0.05). This inhibition caused substantial changes in the inflammatory response of neutrophils. 33% less chemotactic activity was seen in sevoflurane-treated LPS cells (P < 0.001) as well as 47% decreased adhesion of neutrophils to AEC (P < 0.001).


CONCLUSIONS
This study shows that sevoflurane alters the LPS-induced inflammatory response, not only with respect to the expression pattern of inflammatory mediators, but also regarding the biological consequences with less accumulation of effector cells such as neutrophils.
Suter
Dominik
D
Institute of Anesthesiology, University of Zurich, Zurich, Switzerland.
Spahn
Donat R
DR
Blumenthal
Stephan
S
Reyes
Livia
L
Booy
Christa
C
Z'graggen
Birgit Roth
BR
Beck-Schimmer
Beatrice
B
D000777:Anesthetics / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D015846:Monokines / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D000077149:Sevoflurane
D000777:Anesthetics; D018685:Anesthetics, Inhalation; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D004731:Endotoxins; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D008738:Methyl Ethers; D015846:Monokines; D018799:Intercellular Adhesion Molecule-1; D000077149:Sevoflurane