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

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.