SURGICAL STRESS-MEDIATED SUPPRESSION OF MURINE NATURAL-KILLER CELL CYTO-TOXICITY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (9) , 3888-3891
Abstract
Natural killer cell-mediated cytotoxicity (NKCC) is one of several possible immune defense mechanisms that may protect against the development of solid-tumor metastases. In vitro NKCC can be significantly impaired by both surgical stress and progressive tumor burden. Female C57BL/6 mice received a hindfoot amputation under anesthesia with Nembutal i.p. Twenty-four hours later, amputated and control groups were sacrificed, spleens were harvested and cytotoxicity assays were performed using 51Cr-labeled Yac-1 lymphoma target cells. In amputated animals, in vitro NKCC was significantly impaired at 4 effector:target ratios, decreasing by as much as 59%. Nembutal treatment alone caused no significant changes in in vitro NKCC compared to untreated controls. Tumor burden was studied by inoculating the hindfoot pads of C57BL/6 mice with 5 .times. 105 Lewis lung tumor cells. Animal group were sacrificed 24 h, 1 wk and 2 wk after tumor inoculation and the 51Cr release assay was performed. One day and 1 wk of tumor burden mildly stimulated NKCC in vitro; after 2 wk of tumor burden, when lung metastases were detectable, in vitro NKCC was almost totally suppressed compared with non-tumor-bearing controls. Animals bearing tumor for 1 wk and then given amputations showed significantly impaired NKCC in vitro. In vivo, identical animals bearing tumor for 1 wk and then given amputations on sacrifice 1 wk later were found to have a 71% incidence of lung metastases compared with 38% tumor-bearing unstressed controls. Surgical stress and progressive tumor burden independently and codependently impair NKCC in impair NKCC in vitro; this may possibly contribute to the hypermetastatic response observed after surgical stress in this in vivo animal model.