Department of Anesthesia and Perioperative Medicine, Graduate School of Medicine, Ehime University, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan.
Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa 454, Toon City, Ehime, 791-0295, Japan.
Sci Rep. 2024 Aug 20;14(1):19337. doi: 10.1038/s41598-024-69987-z.
General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.
全身麻醉被认为会抑制免疫系统，并对术后感染和癌症的长期预后产生负面影响。然而，全身麻醉诱导的免疫抑制的机制尚不清楚。在这项研究中，我们专注于广泛用于全身麻醉和重症监护镇静的异丙酚，并研究了它对 T 细胞功能和 T 细胞依赖性免疫反应的影响。我们发现，异丙酚抑制 T 细胞糖酵解代谢、向效应 T 细胞分化以及效应 T 细胞产生细胞因子。体外实验中，在异丙酚存在的情况下，激活和分化为效应细胞的 CD8 T 细胞显示出降低的抗肿瘤活性。此外，异丙酚处理抑制了李斯特菌感染期间抗原特异性 CD8 T 细胞数量的增加。相比之下，异丙酚的给药改善了炎性疾病小鼠模型中的炎症状况，如 OVA 诱导的过敏性气道炎症、半抗原诱导的接触性皮炎和实验性变态反应性脑脊髓炎。这些结果表明，异丙酚可能通过抑制 T 细胞功能和 T 细胞依赖性免疫反应来降低肿瘤和感染性免疫，同时通过抑制炎症来改善慢性炎症性疾病的发病机制和预后。
