MECHANISM OF ACTION OF THIABENDAZOLE

该项目的总体科学目标是检验以下假设： 免疫调节剂噻苯咪唑（TBZ），当与 胸腺依赖性抗原，促进非体液免疫的产生， 因子（淋巴造血刺激因子，LHSF），影响 原始淋巴细胞的增殖和分化， 造血细胞 第一年取得了以下进展 的补助金。 我们已经开始实验，以确定是否其他胸腺依赖性 除DNFB外，抗原可与TBS协同作用， 刺激正常小鼠淋巴造血。 结果表明 另一种皮肤致敏抗原恶唑酮也有效，而KLH 并不自由 我们现在计划筛选一组胸腺依赖性抗原， 确定是否只有那些具有皮肤致敏特性的活性物质， LHSF的产生。 这些研究的结果可能 重要的临床意义，如果真的皮肤致敏抗原， TBZ的最大治疗效果所需的和密切相关的 化合物. 我们已经启动了实验，以确定TBZ和DNFB是否刺激 先天性无胸腺（裸）小鼠的淋巴造血。 到目前为止， 未观察到任何影响。 这表明T淋巴细胞可能是重要的 在LHSF的一代。 我们计划正式测试这一点， 正常和裸鼠间的细胞转移和血清转移实验 注射TBZ和/或DNFB。 这些实验还应该揭示 LHSF是否由两种因子组成，一种是由抗原刺激的 T细胞（因此在裸鼠中不存在）和一种由 TBZ刺激的巨噬细胞（因此存在于裸鼠中）。 我们改进了TdT阳性细胞的检测方法， 免疫荧光检测免疫过氧化物酶。 结果不仅更多 可量化，而且制剂是永久性的，可用于 必要时进行回顾性分析。 我们还开展了研究， 50 H-TBZ，TBZ的活性代谢产物。 这将使实验性的 通过消除与高剂量反应系统一起工作的需要， TBZ的不溶性形式。 （意大利）

The general scientific goals of the project are to test the hypothesis that the immunomodulating agent thiabendazole (TBZ), when given in conjunction with a thymus-dependent antigen, promotes the production of ahumoral factor(s) (lymphohemopoietic stimulating factor, LHSF) which affects the proliferation and differentiation of primitive lymphopoietic and hemopoietic cells. The following progress has been made in the first year of the grant. We have initiated experiments to determine whether other thymus-dependent antigens, in addition to DNFB, can act synergistically with TBS to stimulate lymphohemopoiesis in normal mice. The results indicate that oxazolone, another skin-sensitizing antigen, is also effective, whereas KLH is not. We now plan to screen a battery of thymus-dependent antigens to determine if only those having skin-sensitizing properties are active in the generation of the LHSF. The results of these studies may have important clinical implications, if indeed skin-sensitizing antigens are required for the maximum therapeutic efficacy of TBZ and closely related compounds. We have initiated experiments to determine whether TBZ and DNFB stimulate lymphohemopoiesis in congenitally athymic (nude) mice. Thus far we have not observed any effect. This suggests that T lymphocytes may be important in the generation of the LHSF. We plan to formally test this by reciprocal cell transfer and serum transfer experiments between normal and nude mice injected with TBZ and/or DNFB. These experiments should also reveal whether LHSF is composed of two factors, one produced by antigen-stimulated T cells (and therefore absent from nude mice) and one produced by TBZ-stimulated macrophages (and therefore present in nude mice). We have improved the assay for TdT-positive cells by changing from immunofluorescence to immunoperoxidase. The results are not only more quantifiable but also the preparations are permanent and available for retrospective analysis if necessary. We have also initiated studies using 50H-TBZ, the active metabolite of TBZ. This should make the experimental system more dose-responsive by eliminating the need to work with the highly insoluble form of TBZ. (IT)