Fluorinated groups mediate the immunomodulatory effects of volatile anesthetics in acute cell injury.
Volatile anesthetics are known to attenuate inflammatory response and tissue damage markers in acute organ injury. It is unclear whether these beneficial effects of volatile anesthetics are mediated by the ether basic structure or by characteristics of their halogenations. We describe in an in vitro model of acute inflammation in pulmonary cells that halogenation (fluorinated carbon groups) is responsible for the immunomodulatory effects. The inflammatory response after coexposure to endotoxin and sevoflurane, diethyl-ether, or various water-soluble molecules carrying trifluorinated carbon (CF(3)) groups was evaluated in pulmonary epithelial and endothelial cells and in neutrophils. In epithelial and endothelial cells, expression of inflammatory mediators to LPS stimulation was dose-dependently decreased upon exposure to sevoflurane and other molecules with CF(3) groups. This was not observed for diethyl-ether or structure-similar nonfluorinated molecules. In neutrophils, chemotactic activity, as well as expression of surface CD11b and CD62L, was positively modified by molecules carrying CF(3) groups. Cytotoxicity could be excluded. These findings for the first time reveal in an in vitro model of acute inflammation that the immunomodulatory effects are not limited to volatile anesthetics but are associated with a much broader class of CF(3) group-containing molecules. The immunomodulatory effects could now be provided in a hydrophilic, injectable formulation for the treatment of patients suffering from acute organ injury, such as acute lung injury, in environments not suitable for volatile anesthetics.
Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland.
Martin
M
Urner
Ludwig K
LK
Limbach
Inge K
IK
Herrmann
Björn
B
Müller-Edenborn
Birgit
B
Roth-Z'Graggen
Andreas
A
Schlicker
Livia
L
Reyes
Christa
C
Booy
Melanie
M
Hasler
Wendelin J
WJ
Stark
Beatrice
B
Beck-Schimmer
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology; D002244:Carbon / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology; D004926:Escherichia coli / Q000378:metabolism; D005461:Fluorine / Q000494:pharmacology*; D006219:Halogens / Q000737:chemistry; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology; D008833:Microcirculation; D009504:Neutrophils / Q000166:cytology; D051381:Rats; D000077149:Sevoflurane
D000777:Anesthetics; D006219:Halogens; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D008738:Methyl Ethers; D005461:Fluorine; D000077149:Sevoflurane; D002244:Carbon; D053148:Caspase 3