This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by de Rossi, L. W. Articles by Rossaint, R. Search for Related Content PubMed PubMed Citation Articles by de Rossi, L. W. Articles by Rossaint, R. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

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

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

*Department of Anesthesiology, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen; and 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)-B and production of tumor necrosis factor (TNF)- 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- and IL-6 were assayed in the supernatant. Involvement of NF-B was investigated using isolated monocytes from the blood samples. Whole-cell lysates were prepared, and binding of the NF-B p50 and p65 subunit to its target DNA were measured with an enzyme-linked immunosorbent assay-based NF-B kit. LPS-induced production of TNF- and IL-6 as well as activation of NF-B were significantly increased in the presence of xenon compared with controls. In contrast, isoflurane inhibited the activation of NF-B, which was associated with a decreased production of TNF- and IL-6. Our results demonstrate that xenon and isoflurane have opposite effects on the LPS-induced production of TNF- and IL-6. Furthermore, xenon increases, whereas isoflurane inhibits the activation of NF-B, providing a possible molecular mechanism for the different effects on monocyte TNF- 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)-B, whereas isoflurane inhibits LPS-induced activation of NF-B. These findings suggest a possible molecular mechanism for the different effects of both anesthetics on monocyte tumor necrosis factor- and interleukin-6 production.

This article has been cited by other articles:

				Y. Li, X. Zhang, B. Zhu, and Z. Xue Desflurane Preconditioning Inhibits Endothelial Nuclear Factor-{kappa}-B Activation by Targeting the Proximal End of Tumor Necrosis Factor-{alpha} Signaling Anesth. Analg., May 1, 2008; 106(5): 1473 - 1479. [Abstract] [Full Text] [PDF]

				Y. Kidani, T. Taniguchi, H. Kanakura, Y. Takemoto, K. Tsuda, and K. Yamamoto Sevoflurane Pretreatment Inhibits Endotoxin-Induced Shock in Rats Anesth. Analg., October 1, 2005; 101(4): 1152 - 1156. [Abstract] [Full Text] [PDF]