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.
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)-kappaB 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-kappaB was investigated using isolated monocytes from the blood samples. Whole-cell lysates were prepared, and binding of the NF-kappaB p50 and p65 subunit to its target DNA were measured with an enzyme-linked immunosorbent assay-based NF-kappaB kit. LPS-induced production of TNF-alpha and IL-6 as well as activation of NF-kappaB were significantly increased in the presence of xenon compared with controls. In contrast, isoflurane inhibited the activation of NF-kappaB, 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-kappaB, providing a possible molecular mechanism for the different effects on monocyte TNF-alpha and IL-6 production.


CONCLUSIONS
This study has shown that monocytes respond to lipopolysaccharide (LPS) in the presence of xenon with an increased activation of nuclear transcription factor (NF)-kappaB, whereas isoflurane inhibits LPS-induced activation of NF-kappaB. These findings suggest a possible molecular mechanism for the different effects of both anesthetics on monocyte tumor necrosis factor-alpha and interleukin-6 production.
de Rossi
Lothar W
LW
*Department of Anesthesiology, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen; and †Department of Cardiology, University Hospital, Mannheim, Germany.
Brueckmann
Martina
M
Rex
Steffen
S
Barderschneider
Marco
M
Buhre
Wolfgang
W
Rossaint
Rolf
R
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis*; D007530:Isoflurane / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014978:Xenon / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014978:Xenon; D007530:Isoflurane