Effect of dexmedetomidine, midazolam, and propofol on lipopolysaccharide‑stimulated dendritic cells

Guo,Feng; Ding,Ying; Yu,Xue; Cai,Xiujun

doi:10.3892/etm.2018.6094

Effect of dexmedetomidine, midazolam, and propofol on lipopolysaccharide‑stimulated dendritic cells

Authors:
- Feng Guo
- Ying Ding
- Xue Yu
- Xiujun Cai
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Affiliations: Department of Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China, Department of Intensive Care Unit, Sir Run Run Shaw Hospital Xiasha Campus, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China, Department of Medicine, Tengzhou Central People's Hospital, Zaozhuang, Shandong 277500, P.R. China, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
Published online on: April 24, 2018 https://doi.org/10.3892/etm.2018.6094
Pages: 5487-5494

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Abstract

Dexmedetomidine, midazolam and propofol are common sedative drugs used in the intensive care unit. Lipopolysaccharides (LPS) are a potent inducer of human dendritic cells (DCs) maturation and survival, which induces cytokine production. The present study aimed to investigate the effect and mechanisms of sedative drugs on LPS‑induced cytokine production in DCs. The mouse bone marrow‑derived dendritic DC2.4 cell line was used in the present study. The Cell Counting Kit‑8 assay was used to measure the viability of cells. Tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6, and IL‑10 mRNA expression levels and contents were measured using reverse transcription‑quantitative polymerase chain reaction and ELISA, respectively. The expression levels of proteins associated with nuclear factor‑κB (NF‑κB) and mitogen activated protein kinase signaling pathways were assessed by western blotting. The three sedatives had different roles on TNF‑α, IL‑1β, IL‑6, and IL‑10 mRNA expression levels and content in DCs. Dexmedetomidine promoted inflammatory cytokine production at high clinical concentrations (10, 1 and 0.1 µM), however suppressed them at the lowest clinical concentration (0.001 µM), which was associated with NF‑κB and c‑Jun N‑terminal kinase (JNK)‑mitogen‑activated protein kinase (MAPK) signaling. Midazolam inhibited inflammatory cytokine production via suppression of the NF‑κB and JNK signaling pathways. Propofol partly inhibited inflammatory cytokine production, including IL‑1β and IL‑6, and the anti‑inflammatory effect may result from inhibition of JNK‑MAPK, and enhanced NF‑κB and extracellular signal‑regulated kinase‑MAPK signaling at clinical concentrations. The present study helped to elucidate the function of sedatives in LPS‑induced cytokine production in DCs, which will facilitate rational implementation of these sedatives in patients undergoing tracheal intubation with sepsis or multiple organ dysfunction syndrome.

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