CHEM STUDY OF NATL KILLER CELL TOX FOLLOWING SURG STRESS

自然杀伤细胞对肿瘤的细胞毒作用可能是 在防止体内实体瘤扩散方面具有重要作用。 多种动物模型显示肿瘤发生率增加 手术应激后的播散；之前我们观察到 手术压力会损害小鼠的NKCC。因为 手术在实体肿瘤控制中的重要性 对研究外科应激的机制很有价值 NKCC损害。这项研究的结果表明 手术后NKCC的抑制最早在术后2小时开始 小鼠后肢截肢，在4天时达到最低点，但没有 恢复到对照水平，直到术后第23天。麻醉剂 单独治疗并不能引起类似的NKCC抑制。 NKCC的抑制伴双侧脾的改变 大小和形态。免疫抑制被观察到在 多个隔室，包括外周血，骨髓， 还有脾。混合实验表明，手术应激 本身产生了影响NKCC的抑制细胞群； 校准的出血不会产生类似的抑制 NKCC。观察到的抑制显然需要细胞到细胞 从4小时和18小时的抑制子培养上清开始接触 细胞没有引起抑制。观察到的抑制是 用干扰素诱导围手术期治疗预防 吡啶酮类似物2-氨基-5-溴-6-苯基-4-嘧啶醇 (ABPP)。这些临床前的观察指向了NK的未来 围手术期特异性免疫疗法可能有助于预防 可能的肿瘤扩散发生在 做手术。

Natural killer cell cytotoxicity (NKCC) against tumor may be important in preventing in vivo solid tumor dissemination. Multiple animal models demonstrate increased rates of tumor dissemination after surgical stress; previously we have observed that surgical stress impairs murine NKCC. Because of the importance of surgery in the control of solid tumor it may be valuable to examine the mechanism underlying surgical stress impairment of NKCC. Result of this research demonstrate that post surgical suppression of NKCC began as early as 2 hr after murine hind limb amputation, reached nadir at 4 days, and did not recover to control level until postoperative day 23. Anesthetic treatment alone did not cause comparable NKCC suppression. The suppression of NKCC accompanied changes in both splenic size and morphology. The immune suppression was observed in multiple compartments, including peripheral blood, bone marrow, and spleen. Mixing experiments demonstrated that surgical stress per se generated a suppressor cell population affecting NKCC; calibrated bleeding did not generate comparable suppression of NKCC. The observed suppression apparently required cell-to-cell contact since supernatants from 4 and 18 hr cultures of suppressor cells did not cause suppression. The observed suppression was prevented by perioperative treatment with the interferon inducing pyrimdinone analog 2-amino-5-bromo-6-phenyl-4-pyrimidinol (ABPP). These preclinical observations point to the future of NK specific perioperative immunotherapy that may help prevent possible tumor dissemination from occurring at the time of surgery.