Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People's Republic of China.
Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Central North Road, Wenzhou 325035, People's Republic of China.
Int Immunopharmacol. 2021 Jun;95:107480. doi: 10.1016/j.intimp.2021.107480. Epub 2021 Mar 3.
Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist, which can regulate inflammatory responses. However, whether DEX interferes with the inflammation resolving remains unclear. Here, we reported the effects of DEX on zymosan-induced generalized inflammation in mice during resolution. Mice were administered intraperitoneally with DEX after the initiation of sepsis. The resolution interval (Ri), a vital resolution indice, decreased from twelve hours to eight hours after the administration of DEX. The induction of peritoneal pro-inflammatory interleukin [IL] - 1β and tumour necrosis factor-α (TNF-α) appeared to be inhibited. Of interest, the anti-inflammatory transforming growth factor-β1 (TGF-β1) but not IL-10 levels were up-regulated at twenty-four hours in the DEX group along with 1.0 mg/mice zymosan A (ZyA) treatment. The expression levels of multiple genes related to protective immune processes and clearance functions were detected and revealed the same trends. DEX markedly increased the F4/80Ly6G macrophage population. Additionally, the adequate apoptotic neutrophil clearance from injury after DEX installation could be reverse by opsonization or co-instillation of TGF-β1 neutralizing antibody in vivo, promoting the inflammation-resolution programs. In conclusion, DEX post-treatment, via the increase of F4/80Ly6G macrophages, provokes further secretion of TGF-β1, leading to the attenuated cytokine storm and accelerated inflammation resolving.
右美托咪定（DEX）是一种高选择性的α2-肾上腺素能受体激动剂，可调节炎症反应。然而，DEX 是否干扰炎症消退仍不清楚。在这里，我们报道了 DEX 在解决期间对酵母聚糖诱导的小鼠全身性炎症的影响。在脓毒症开始后，通过腹腔内给予小鼠 DEX。DEX 给药后，缓解间隔（Ri），一个重要的缓解指标，从 12 小时缩短到 8 小时。诱导的腹腔促炎白细胞介素 [IL]-1β和肿瘤坏死因子-α（TNF-α）似乎被抑制。有趣的是，在 DEX 组中，抗炎转化生长因子-β1（TGF-β1）而不是 IL-10 水平在 24 小时时上调，同时给予 1.0mg/mice 酵母聚糖 A（ZyA）处理。还检测了与保护性免疫过程和清除功能相关的多个基因的表达水平，并显示出相同的趋势。DEX 明显增加了 F4/80Ly6G 巨噬细胞群。此外，DEX 给药后，通过增加 F4/80Ly6G 巨噬细胞，进一步引发 TGF-β1 的分泌，从而减弱细胞因子风暴并加速炎症消退。总之，DEX 治疗后，通过增加 F4/80Ly6G 巨噬细胞，进一步引发 TGF-β1 的分泌，从而减弱细胞因子风暴并加速炎症消退。
