Mechanism of Surgical Stress Impairment of Human Perioperative Natural Killer Cell Cytotoxicity

Abstract

Natural killer (NK) cells are an important defense against intravascular tumor dissemination. Tumor embolization can occur at surgery, so we tested whether surgical stress decreased perioperative NK cell cytotoxicity, and examined the underlying mechanism of suppression. Patients with solid tumors underwent NK cell cytotoxicity assay just before and 24 hours after surgery in a 3-hour chromium 51 release assay. The NK cell cytotoxicity was significantly decreased postoperatively. We considered that surgical NK cell impairment might be due to (1) NK cell redistribution, (2) presence of suppressor cells, or (3) direct "toxic" effects on NK cells. Impaired NK cell cytotoxicity was not due to NK cell redistribution, because differential counts showed no significant changes in the percentage of large granular lymphocyte NK morphology. To isolate possible suppressor cells, postoperative cells from patients were selectively depleted of NK cells using anti-Leu-11b monoclonal antibody plus complement; these cells were then mixed with autologous preoperative cells. Postoperative NK cell cytotoxicity was markedly impaired, but the postoperative NK depleted cells did not suppress preoperative NK cells. We conclude that NK cell functional impairment from surgical stress is due to direct "toxic" effects on NK cells rather than either NK cell redistribution or the generation of NK-directed suppressor cells.

Timing within the menstrual cycle, sex, and the use of oral contraceptives determine adrenergic suppression of NK cell activity

“…We also suggest that adrenergic suppression of NK activity may be a mechanism contributing to the adverse effects of surgery. Suppression of NK activity after surgery is well documented clinically (Pollock et al, 1991;Brittenden et al, 1996), was attributed by animal studies to adrenergic mechanisms (Ben-Eliyahu, 1998a), and was suggested by human and animal studies to promote metastasis (Zoller et al, 1989;Pollock et al, 1991;Taketomi et al, 1998;Ben-Eliyahu et al, 1999). The current study demonstrated that such adrenergic suppression is also modulated by the menstrual cycle, thus proposing this modulation as a mechanism contributing to the clinical phenomena.…”

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation

“…The immunosuppressive effects of surgical and anesthetic intervention include impaired T cell proliferation (39), decreased natural killer cell cytotoxicity (43), and altered phagocytic cell function (5,23). After surgery, the imbalance between pro-and anti-inflammatory cytokines released by monocytes and macrophages may promote dysfunction of innate cellular immunity and increased susceptibility to infection (35,59).…”

Comparison between interstitial laser thermotherapy and excision of an adenocarcinoma transplanted into rat liver

“…Owing to its ability to seal vessels, it is possible that laser thermotherapy gives less intravascular tumour cell spread than surgical resection. Surgery has been shown to cause generalized immunosuppression, including depressed function of immune cells, such as lymphocytes, NK cells and non-parenchymal cells of the liver, which have the capacity to kill tumour cells (Pearson et al, 1986;Pollock et al, 1987Pollock et al, , 1992Colachio et al, 1994;Oka et al, 1994). Surgical resection also induces the production and release of growth factors, events that may stimulate cell division of tumours and facilitate recurrence and spread (Goustin et al, 1986;Fisher et al, 1989;Davies et al, 1994).…”