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Fluorinated groups mediate the immunomodulatory effects of volatile anesthetics in acute cell injury


Urner, M; Limbach, L K; Herrmann, I K; Müller-Edenborn, B; Roth-Z'Graggen, B; Schlicker, A; Reyes, L; Booy, C; Hasler, M; Stark, W J; Beck-Schimmer, B (2011). Fluorinated groups mediate the immunomodulatory effects of volatile anesthetics in acute cell injury. American Journal of Respiratory Cell and Molecular Biology, 45(3):617-624.

Abstract

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Institute of Anesthesiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:27 Dec 2011 15:59
Last Modified:05 Apr 2016 15:18
Publisher:American Thoracic Society
ISSN:1044-1549
Publisher DOI:10.1165/rcmb.2010-0451OC
PubMed ID:21239603
Permanent URL: http://doi.org/10.5167/uzh-53948

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