Tazawa Kazumasa, Koutsogiannaki Sophia, Chamberlain Matthew, Yuki Koichi
Department of Anesthesiology, Perioperative and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA 02115, USA; Department of Anesthesia, Saitama Medical School, Saitama 350-8550, Japan.
Department of Anesthesiology, Perioperative and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA 02115, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA.
Toxicol Lett. 2017 Jan 15;266:23-31. doi: 10.1016/j.toxlet.2016.12.007. Epub 2016 Dec 8.
A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anesthetics-based general anesthesia. However, the underlying mechanism is yet to be determined. Because natural killer (NK) cells are implicated as important immune cells for tumor recurrence/metastasis in the perioperative period, we examined the effect of different anesthetics on NK cell-mediated tumor cytotoxicity. Because adhesion molecule leukocyte function-associated antigen-1 (LFA-1) is functionally important in NK cells and is inhibited by commonly used volatile anesthetics isoflurane and sevoflurane, we hypothesized that these anesthetics would attenuate NK cell-mediated cytotoxicity. Using human NK cell line NK92-MI cells and tumor cell line K562 cells as a model system, we performed cytotoxicity, proliferation, conjugation and degranulation assays. Lytic granule polarization was also assessed. We showed that isoflurane, sevoflurane and LFA-1 inhibitor BIRT377 attenuated cytotoxicity, and reduced conjugation and polarization, but not degranulation of NK cells. Our data suggest that isoflurane and sevoflurane attenuated NK cell-mediated cytotoxicity at least partly by their LFA-1 inhibition in vitro. Whether or not isoflurane and sevoflurane attenuate NK cell-mediated tumor cytotoxicity in patients needs to be determined in the future.
多项回顾性研究表明，手术肿瘤切除过程中麻醉药物的选择可能会影响肿瘤复发/转移或患者的预后。最近的研究表明，与基于静脉麻醉药的全身麻醉相比，基于挥发性麻醉药的全身麻醉与更差的预后相关。然而，其潜在机制尚待确定。由于自然杀伤（NK）细胞被认为是围手术期肿瘤复发/转移的重要免疫细胞，我们研究了不同麻醉药对NK细胞介导的肿瘤细胞毒性的影响。由于黏附分子白细胞功能相关抗原-1（LFA-1）在NK细胞中具有重要功能，且常用的挥发性麻醉药异氟烷和七氟烷可抑制该分子，我们推测这些麻醉药会减弱NK细胞介导的细胞毒性。我们使用人NK细胞系NK92-MI细胞和肿瘤细胞系K562细胞作为模型系统，进行了细胞毒性、增殖、结合和脱颗粒试验。还评估了溶细胞颗粒极化情况。我们发现异氟烷、七氟烷和LFA-1抑制剂BIRT377减弱了细胞毒性，减少了结合和极化，但未影响NK细胞的脱颗粒。我们的数据表明，异氟烷和七氟烷在体外至少部分通过抑制LFA-1减弱了NK细胞介导的细胞毒性。异氟烷和七氟烷是否会减弱患者体内NK细胞介导的肿瘤细胞毒性，有待未来确定。
