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Ketamine Inhibits Transcription Factors Activator Protein 1 and Nuclear Factor-κB, Interleukin-8 Production, as well as CD11b and CD16 Expression: Studies in Human Leukocytes and Leukocytic Cell Lines

Abstract : Background: Recent data indicate that ketamine exerts antiinflammatory actions. However, little is known about the signaling mechanisms involved in ketamine-induced immune modulation. In this study, we investigated the effects of ketamine on lipopolysaccharide-induced activation of transcription factors activator protein 1 (AP-1) and nuclear factor-kappaB (NF-kappaB) in human leukocyte-like cell lines and in human blood neutrophils. Methods: Electric mobility shift assays were used to investigate ketamine's effects on nuclear binding activity of both transcription factors in U937 cells, and a whole blood flow cytometric technique was used for AP-1 and NF-kappaB determination in leukocytes. Cell lines with different expression patterns of opioid and N-methyl-D-aspartate receptors were used for reverse transcription-polymerase chain reaction to investigate receptors involved in ketamine signaling. Ketamine's effect on interleukin-8 production was assessed in a whole blood assay. Results: Ketamine inhibited both transcription factors in a concentration-dependent manner. These effects did not depend on opiate or N-methyl-D-aspartate receptors. Ketamine also reduced interleukin-8 production in whole blood and expression of CD11b and CD16 on neutrophils. Conclusion: The immunoinhibitory effects of ketamine are at least in part caused by inhibition of transcription factors NF-kappaB and AP-1, which regulate production of proinflammatory mediators. However, signaling mechanisms different from those present in the central nervous system are responsible for ketamine-mediated immunomodulation.
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https://www.hal.inserm.fr/inserm-03543857
Contributor : Yannick Goumon Connect in order to contact the contributor
Submitted on : Wednesday, January 26, 2022 - 11:56:42 AM
Last modification on : Friday, August 26, 2022 - 4:12:26 PM
Long-term archiving on: : Wednesday, April 27, 2022 - 6:43:29 PM

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Ingeborg Welters, Georg Hafer, Axel Menzebach, Jörg Mühling, Christoph Neuhäuser, et al.. Ketamine Inhibits Transcription Factors Activator Protein 1 and Nuclear Factor-κB, Interleukin-8 Production, as well as CD11b and CD16 Expression: Studies in Human Leukocytes and Leukocytic Cell Lines. Anesthesia & Analgesia, Lippincott, Williams & Wilkins, 2010, 110 (3), pp.934-941. ⟨10.1213/ANE.0b013e3181c95cfa⟩. ⟨inserm-03543857⟩

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