title: The effect of different anesthetics on tumor cytotoxicity by natural killer cells.
abstract: 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.
authors.affiliation: 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. Electronic address: kazumasa.tazawa@childrens.harvard.edu.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Tazawa
authors.affiliation: 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. Electronic address: sophia.koutsogiannaki@childrens.harvard.edu.
authors.forename: Sophia
authors.initials: S
authors.lastname: Koutsogiannaki
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: matthew.chamberlain@childrens.harvard.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Chamberlain
authors.affiliation: 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. Electronic address: koichi.yuki@childrens.harvard.edu.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yuki
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053804:Granzymes / Q000187:drug effects; D006801:Humans; D048289:Imidazolidines / Q000633:toxicity*; D007530:Isoflurane / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D008738:Methyl Ethers / Q000633:toxicity*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; C400461:BIRT 377; D048289:Imidazolidines; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane; D053804:Granzymes
keywords: Leukocyte function-associated antigen-1; Natural killer cell; Tumor recurrence/metastasis; Volatile anesthetic