研究组胺对C5 7BL/ 6小鼠脾源性LAK细胞体内杀伤活性的调控作用及可能的机理。方法 :以B16恶性黑色素瘤肺转移的C5 7BL/ 6小鼠作为治疗对象 ,比较LAK/IL 2 /组胺疗法与LAK/IL 2疗法导致的近期疗效和远期疗效之间的差异。结果 :组胺可明显增强LAK/IL 2疗法的体内抗肿瘤转移活性 ,产生明显的肿瘤消退 ,近期疗效优于LAK/IL 2疗法 ;组胺与单纯LAK/IL 2治疗相比 ,LAK/IL 2 /组胺疗法显著提高了荷B16恶性黑色素瘤小鼠的生存时间和生存率 ,具有较好的远期疗效 ;组胺的这一协同效应可被H2 受体拮抗剂雷尼替丁完全阻断 ,H2 受体激动剂dimaprit则可模拟这一效应。结论 :用组胺和LAK/IL 2联合应用在C5 7BL/ 6小鼠体内具有较强的协同效应 ,对B16恶性黑色素瘤细胞的杀伤效果明显优于传统的LAK/IL 2疗法 ;组胺的这一效应是通过体内单核巨噬细胞上的组胺H2 受体介导的。

Objective: To investigate the role and mechanism of histamine in regulation of C57BL/6 mice spleen derived LAK activity in vivo. Methods: The C57BL/6 mice carrying B16 pulmonary metastatic melanoma were treated with LAK/IL 2/histamine therapy or LAK/IL 2 therapy with the aim of evaluating both anti tumor responses in vivo. Results: It was found that the addition of histamine effectively potentiated the anti metastatic effect produced by LAK/IL 2 therapy and induced regression of NK resistant B16 pulmonary metastatic melanoma. Survival period was significantly prolonged in mice receiving LAK/IL 2/histamine as compared with LAK/IL 2 therapy alone. The effect of histamine was completely blocked by H 2 R antagonist ranitidine, and mimicked by dimaprit, a H 2 R agonist. Conclusion:Histamine, via specific activation of H 2 R, may be an important regulator of LAK cells activity; histamine and LAK/IL 2 synergistically induce more potent antitumor efficacy in vivo .