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.

Background-Previously we have shown that volatile anesthetic isoflurane attenuated neutrophil recruitment and phagocytosis in mouse sepsis and skin inflammation models. The objectives of this study were to test ex vivo function of neutrophils in patients who underwent cardiac catheterization under volatile anesthesia versus intravenous anesthesia (IA), and also to assess the effect of anesthesia on surgical site infections (SSIs) using mouse model to understand the clinical relevance of anesthesia-induced immunomodulation. Methods-Whole blood from patients who underwent cardiac catheterization procedures either by volatile anesthesia or IA was collected and subjected to phagocytosis assay and a lipopolysaccharide-induced tumor necrosis factor-α assay. Mouse SSI with Staphylococcus aureus USA300 was created, and the effect of isoflurane and propofol exposure (short or long exposure) on bacterial loads was tested. Results-Neutrophil phagocytosis was significantly attenuated after the induction of volatile anesthesia in patients, but not by IA. Monocyte phagocytosis was not affected by the anesthesia regimen. Bacterial loads following SSIs were significantly higher in mice receiving long, but not short, isoflurane exposure. Propofol exposure did not affect bacterial loads. Discussion-Neutrophil phagocytosis can be affected by the type of anesthesia, and preclinical model of SSIs showed potential clinical relevance. The effects of anesthesia regimen on SSIs in patients needs to be studied extensively in the future.

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