Dexmedetomidine, an α2-adrenergic/imidazoline receptor agonist, is a widely used intravenous anesthetic. Its primary current usage is for sedation of patients in the intensive care unit. The mouse air pouch model is versatile in studying the anti-inflammatory effect of a drug on a local inflammation, which is induced by a variety of substances. In the present study, using the carrageenan-induced air pouch inflammation model, we tested whether dexmedetomidine mitigates inflammation occurring locally in the mouse air pouch. We found that dexmedetomidine dose-dependently inhibited the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pouch and decreased the number of white blood cells (WBC) recruited into the pouch. Dexmedetomidine also dose-dependently inhibited the production of neutrophil chemokines, cxcl1 and cxcl2. Furthermore, the dexmedetomidine-induced decreased recruitment of WBC into the pouch was successfully reversed with intra-pouch administration of cxcl1/cxcl2, but not TNF-α or IL-6. Lastly, the inhibition of the production of the cytokines and chemokines with dexmedetomidine was reversed by the treatment of yohimbine, suggesting that dexmedetomidine's anti-inflammatory effect is primarily via the stimulation of the α2-adrenergic receptor. We conclude that dexmedetomidine has an anti-inflammatory property in the carrageenan-induced mouse air pouch inflammation model, and that the dexmedetomidine-induced inhibition of production of the neutrophil chemokines, cxcl1 and cxcl2, may be related, at least in part, to the inhibition of WBC intra-pouch recruitment.
Keywords: Chemokine; cytokine; dexmedetomidine; inflammation; neutrophil.