Department of Anaesthesiology, University Medical Centre Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands.
Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen (UMCG), University of Groningen, 9713 GZ Groningen, The Netherlands.
Int J Mol Sci. 2024 Oct 14;25(20):11045. doi: 10.3390/ijms252011045.
Only some subpopulations of natural killer (NK) cells have cytotoxic functionality, and the effects of anesthetics on these subpopulations are unknown. This study aimed to evaluate the in vitro effects of various anesthetics, both alone and in combination, on the distribution and cytotoxic function of NK cells and their subpopulations. Peripheral blood mononuclear cells (PBMCs) from eight healthy volunteers were treated for 4 h in vitro with dexmedetomidine, remifentanil, lidocaine, propofol, sevoflurane, and combinations in clinically relevant concentrations or left untreated. Flow cytometry was used to quantify the percentage of sampled NK cells and evaluate their distribution (CD56CD16, CD56CD16, CD56CD16, CD56CD16, and CD56CD16) and cytotoxicity (Granzyme B (GrzB) and perforin) of NK cell subpopulations. Although the percentage of total NK cells did not change following exposure to anesthesia, the most important cytotoxic subpopulation (CD56CD16 NK cells) decreased after exposure to both propofol (-3.58%, = 0.045) and sevoflurane (-16.10%, = 0.008) alone, and most combinations, especially in combination with lidocaine (propofol with lidocaine (-9.66%, = 0.002) and sevoflurane with lidocaine (-21.90%, < 0.001)). Dexmedetomidine and remifentanil had no effect on CD56CD16 NK cells. Furthermore, no anesthetic regimen or combination altered the expression of GrzB and perforin in NK cells or NK cell subpopulations. In short, propofol and sevoflurane suppressed the highly cytotoxic phenotype (CD56CD16) of NK cells, with those exposed to sevoflurane combinations showing greater reductions. Immunosuppression was intensified with the inclusion of lidocaine in the anesthetic regimen.
只有一些自然杀伤 (NK) 细胞亚群具有细胞毒性功能，而麻醉剂对这些亚群的影响尚不清楚。本研究旨在评估不同麻醉剂单独或联合使用对 NK 细胞及其亚群分布和细胞毒性功能的体外影响。从 8 名健康志愿者的外周血单核细胞 (PBMC) 中分离出 NK 细胞，在体外与右美托咪定、瑞芬太尼、利多卡因、丙泊酚、七氟醚以及临床相关浓度的组合处理 4 小时，或不做处理。采用流式细胞术检测 NK 细胞的百分比，并评估其分布（CD56CD16、CD56CD16、CD56CD16、CD56CD16 和 CD56CD16）和 NK 细胞亚群的细胞毒性（颗粒酶 B (GrzB) 和穿孔素）。尽管暴露于麻醉后总 NK 细胞的百分比没有变化，但最重要的细胞毒性亚群（CD56CD16 NK 细胞）在单独接触丙泊酚 (-3.58%， = 0.045) 和七氟醚 (-16.10%， = 0.008) 以及大多数组合后减少，尤其是与利多卡因联合使用时（丙泊酚与利多卡因 (-9.66%， = 0.002) 和七氟醚与利多卡因 (-21.90%， < 0.001)）。右美托咪定和瑞芬太尼对 CD56CD16 NK 细胞没有影响。此外，没有任何麻醉方案或组合改变 NK 细胞或 NK 细胞亚群中 GrzB 和穿孔素的表达。简而言之，丙泊酚和七氟醚抑制 NK 细胞的高细胞毒性表型（CD56CD16），而暴露于七氟醚组合的细胞则表现出更大的降低。当将利多卡因纳入麻醉方案中时，免疫抑制作用会加剧。
