组按联合LAK／IL—2疗法治疗转移性黑色素瘤

目的：研究组胺对C57BL／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C57BL／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C57BL／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。

Combination with Histamine and LAK/IL-2 Therapy for the Treatment of Metastatic Melanoma

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 .