MECHANISM OF ACTION OF THIABENDAZOLE

该项目的总体科学目标是检验这一假设 免疫调节剂噻苯咪唑(TBZ)，当联合给药时 与胸腺依赖抗原一起，促进非体液细胞的产生 S(淋巴造血刺激因子，LHSF) 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 拨款的一部分。 我们已经开始实验，以确定其他依赖胸腺的 除DNFB外，抗原还可以与TBS协同作用，从而 刺激正常小鼠的淋巴造血。结果表明，该系统具有较高的可靠性。 另一种皮肤致敏抗原恶唑酮也是有效的，而KLH 不是的。我们现在计划筛选一组胸腺依赖抗原，以 确定是否只有那些具有皮肤敏感特性的产品才在 LHSF的诞生。这些研究的结果可能会 重要的临床意义，如果皮肤致敏抗原确实是 为达到最大的治疗效果所必需的，并且密切相关 化合物。 我们已经开始了实验，以确定TBZ和DNFB是否会刺激 先天性无性体(裸鼠)小鼠的淋巴造血。到目前为止，我们已经 没有观察到任何效果。这表明T淋巴细胞可能很重要 在LHSF的产生过程中。我们计划通过互惠正式测试这一点 正常小鼠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是否由两个因素组成，一个是由抗原刺激产生的 T细胞(因此在裸鼠中不存在)和一种由 TBZ刺激的巨噬细胞(因此存在于裸鼠体内)。 我们已经改进了TDT阳性细胞的检测方法，从 免疫过氧化物酶的免疫荧光。结果不仅是更多 但也是可以量化的，而且准备工作是永久性的，可以用于 必要时进行回顾分析。我们还启动了研究，使用 TBZ的活性代谢物50H-TBZ。这应该使试验性的 系统不再需要与高度 不溶形式的TBZ。(IT)

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)