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
- 1 March 2010
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Anesthesia & Analgesia
- Vol. 110 (3), 934-941
- https://doi.org/10.1213/ane.0b013e3181c95cfa
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-κB (NF-κB) 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-κB 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-κB 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.Keywords
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