Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway

• Published in: International immunopharmacology 2016-06, Vol.35, p.210-216
• Main Authors: Liu, Zhaoguo, Wang, Yueping, Wang, Yaoqi, Ning, Qiaoqing, Zhang, Yong, Gong, Chunzhi, Zhao, Wenxiang, Jing, Guangjian, Wang, Qianqian
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists - therapeutic use; alpha7 Nicotinic Acetylcholine Receptor - antagonists & inhibitors; Animals; Anti-Inflammatory Agents - therapeutic use; Bungarotoxins - administration & dosage; Bungarotoxins - pharmacology; Cholinergic anti-inflammatory pathway; Dexmedetomidine; Dexmedetomidine - therapeutic use; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lipopolysaccharides; Lipopolysaccharides - immunology; Lung; Lung - drug effects; Lung - immunology; Male; Mice; Mice, Inbred BALB C; NF-kappa B - metabolism; Pneumonia - drug therapy; Sepsis; Sepsis - drug therapy; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2016.04.003

Dexmedetomidine (Dex) is a highly selective α2-adrenergic receptor agonist that is widely used for sedation in intensive care units and in clinical anesthesia. Dex has also been shown to possess anti-inflammatory benefits. However, the underlying mechanism by which Dex relieves the inflammatory reaction in the lung tissues of septic mice has not been fully elucidated. In this study, we aimed to evaluate the protective effects and possible mechanism of Dex on the sepsis-induced lung inflammatory response in mice. Sepsis was induced in mice models through the intraperitoneal injection of lipopolysaccharide (LPS). The preemptive administration of Dex substantially abated sepsis-induced pulmonary edema, pulmonary histopathological changes, and NF-κB p65 activity. The production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both the mRNA and protein levels was also reduced. Moreover, these effects were significantly blocked by the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist α-bungarotoxin (α-Bgt). α-Bgt aggravated pulmonary edema and pulmonary histopathological changes, as well as increased NF-κB p65 activity and TNF-α and IL-6 expression at both the mRNA and protein levels. The overall results demonstrate that Dex inhibits the LPS-induced inflammatory reaction in the lung tissues of septic mice partly through the α7nAChR-dependent cholinergic anti-inflammatory pathway. •Dexmedetomidine inhibits the TNF-α and IL-6 at both the mRNA and protein levels.•α-Bungarotoxin reverses dexmedetomidine-induced decrease in NF-κBp65 activation.•α-Bungarotoxin reverses the protective effects of dexmedetomidine on septic mice.•Dexmedetomidine inhibits lung inflammatory through the cholinergic anti-inflammatory pathway.