Gordon W C, Prager M D
J Natl Cancer Inst. 1978 Aug;61(2):415-21.
Levamisole enhanced transformation of murine lymphocytes stimulated either by mitogens or allogeneic lymphocytes. In a similar dose-dependent pattern it stimulated in vitro growth of L1210, P1798, and 6C3HED but not YAC lymphoma cells. Stimulation of growth of lymphoma cells was greater by peritoneal cells harvested from normal mice 4 days after levamisole injection than by peritoneal cells from untreated mice. This effect correlated with the shortened survival time of BALB/c mice treated with levamisole prior to P1798 implantation compared to that of a control group not pretreated. Administration of levamisole with iodoacetamide-modified tumor cells in immunoprophylaxis studies had no effect on the rejection of a tumor implant or on development of tumor-specific antibody. Levamisole was added to regimens involving asparaginase therapy of 6C3HED-bearing C3H mice and chemoimmunotherapy of BALB/c mice bearing P1798 with methotrexate and iodoacetamide-modified P1798 cells. In neither case were there increased numbers of survivors, and mean survival time was generally decreased for the levamisole-treated groups. The stimulated tumor growth may have been mediated by a direct effect of levamisole on the lymphoma cells, through an effect on other cell types, or by both effects; these effects apparently outweighed potentially beneficial effects of levamisole on the immune system.
左旋咪唑可增强由丝裂原或同种异体淋巴细胞刺激的小鼠淋巴细胞的转化。它以类似的剂量依赖性模式刺激L1210、P1798和6C3HED细胞的体外生长,但不刺激YAC淋巴瘤细胞。注射左旋咪唑4天后从正常小鼠采集的腹腔细胞对淋巴瘤细胞生长的刺激作用大于未处理小鼠的腹腔细胞。这种效应与P1798植入前用左旋咪唑处理的BALB/c小鼠与未预处理的对照组相比生存时间缩短相关。在免疫预防研究中,将左旋咪唑与碘乙酰胺修饰的肿瘤细胞一起给药,对肿瘤植入物的排斥或肿瘤特异性抗体的产生没有影响。将左旋咪唑添加到涉及对携带6C3HED的C3H小鼠进行天冬酰胺酶治疗以及对携带P1798的BALB/c小鼠用甲氨蝶呤和碘乙酰胺修饰的P1798细胞进行化学免疫治疗的方案中。在这两种情况下,存活者数量均未增加,并且左旋咪唑处理组的平均生存时间通常缩短。刺激肿瘤生长可能是由左旋咪唑对淋巴瘤细胞的直接作用、对其他细胞类型的作用或两者共同作用介导的;这些作用显然超过了左旋咪唑对免疫系统的潜在有益作用。