宮田 拓馬

We aimed to determine whether subcutaneous injection of recombinant canine interferon-γ (rCaIFN-γ) 1h before general anesthesia with a combination of propofol and isoflurane (P-I) changes the cytotoxic activity of natural killer (NK) cells during anesthesia in dogs. Nine clinically healthy beagles were assigned to one of two groups: rCaIFN-γ-treated group (n=5) and control group (no treatment, n=4). One hour before P-I anesthesia, rCaIFN-γ was subcutaneously injected at a dose of 1×104U/kg body weight for the test group and physiologic saline was subcutaneously injected for the control group. Blood samples were collected 1h before P-I anesthesia (immediately before rCaIFN-γ injection) and 1 and 3h after anesthesia induction. NK cytotoxic activity was measured using the Rose Bengal assay, using canine thyroid adenocarcinoma cells as target cells. In the control group, NK cytotoxic activity decreased significantly over time (P<0.05). On the other hand, in the rCaIFN-γ group, the activity increased for the first hour after anesthesia induction without a significant difference from the level before anesthesia; furthermore, the activity at 3h after anesthesia induction was comparable with that before anesthesia. NK cytotoxic activity at 1 and 3h after anesthesia induction was significantly higher in the rCaIFNγ group than in the control group (P<0.05). Subcutaneous injection of rCaIFN-γ 1h before P-I general anesthesia not only maintained but also enhanced NK cytotoxic activity up to 3h after anesthesia induction in dogs. In conclusion, subcutaneous injection of rCaIFN-γ before cancer resection in cancer-bearing dogs might be effective for preventing intraoperative dissemination of cancer cells and postoperative cancer recurrence and metastasis.

To investigate influence of general anesthesia on immunological anti-tumor activity, the natural killer (NK) cytotoxic activity of peripheral lymphocytes (PBLs) was measured in 7 dogs anesthetized for 3 hr with isoflurane following propofol-induction (anesthesia group) and 6 dogs without anesthesia (control group). Blood samples were collected before (baseline) and 24, 120 and 192 hr after the anesthesia. The PBLs were isolated via centrifugation with Ficoll-Hypaque solution (density, 1.073), and adherent cells were removed. The NK cytotoxic activity of the isolated PBLs against canine thyroid cancer cells was detected by the colorimetric rose Bengal assay. Significant decrease in the NK cytotoxic activity was observed at 24 hr after the anesthesia, compared with the baseline values and the control group. The NK cytotoxic activities were recovered to the baseline values until 120 hr after the anesthesia. The general anesthesia with isoflurane following propofol-induction decreased the NK cytotoxic activities of PBLs in dogs. This finding has a clinical relevance to the risk of tumor recurrence or metastasis induced by the suppression of immunological anti-tumor activity after general anesthesia in dogs. The results further emphasized the importance of the need to evaluate immune suppression following general anesthesia in animals.