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Anesth Analg 2004;98:1007-1012
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000106860.27791.44


ANESTHETIC PHARMACOLOGY

Xenon and Isoflurane Differentially Modulate Lipopolysaccharide-Induced Activation of the Nuclear Transcription Factor KB and Production of Tumor Necrosis Factor-{alpha} and Interleukin-6 in Monocytes

Lothar W. de Rossi*, Martina Brueckmann{dagger}, Steffen Rex*, Marco Barderschneider*, Wolfgang Buhre*, and Rolf Rossaint*

*Department of Anesthesiology, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen; and {dagger}Department of Cardiology, University Hospital, Mannheim, Germany

Address correspondence and reprint requests to Lothar W. de Rossi, MD, Department of Anesthesiology, University Hospital, Aachen Pauwelsstr, 30, D-52074 Aachen, Germany. Address e-mail to Lderossi{at}ukaachen.de

Anesthetics are known to interfere with the production of inflammatory cytokines. In this study, we investigated the effect of xenon and isoflurane on the lipopolysaccharide (LPS)-induced activation of the nuclear transcription factor (NF)-{kappa}B and production of tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 in vitro. Whole blood was incubated with LPS in the absence or presence of the either xenon (30 and 60 Vol%) and isoflurane (1 and 2 minimum alveolar anesthetic concentration [MAC]). After 4 h, TNF-{alpha} and IL-6 were assayed in the supernatant. Involvement of NF-{kappa}B was investigated using isolated monocytes from the blood samples. Whole-cell lysates were prepared, and binding of the NF-{kappa}B p50 and p65 subunit to its target DNA were measured with an enzyme-linked immunosorbent assay-based NF-{kappa}B kit. LPS-induced production of TNF-{alpha} and IL-6 as well as activation of NF-{kappa}B were significantly increased in the presence of xenon compared with controls. In contrast, isoflurane inhibited the activation of NF-{kappa}B, which was associated with a decreased production of TNF-{alpha} and IL-6. Our results demonstrate that xenon and isoflurane have opposite effects on the LPS-induced production of TNF-{alpha} and IL-6. Furthermore, xenon increases, whereas isoflurane inhibits the activation of NF-{kappa}B, providing a possible molecular mechanism for the different effects on monocyte TNF-{alpha} and IL-6 production.

IMPLICATIONS: This study has shown that monocytes respond to lipopolysaccharide (LPS) in the presence of xenon with an increased activation of nuclear transcription factor (NF)-{kappa}B, whereas isoflurane inhibits LPS-induced activation of NF-{kappa}B. These findings suggest a possible molecular mechanism for the different effects of both anesthetics on monocyte tumor necrosis factor-{alpha} and interleukin-6 production.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2004 by the International Anesthesia Research Society.