IFN-ALPHA AND IL-2 INDUCED PROLIFERATION OF LYMPHOID CELLS IN VIVO

为了了解协同抗肿瘤作用的机制，我们有 检测小鼠体内不同器官中淋巴细胞的增殖情况 对IL-2和干扰素-α的反应。我们利用了一种技术 用125-IUdR标记体内新合成的DNA 内源性细胞的增殖。在4天的IL-2治疗后， 观察到125-IUdR在肺、肝、肾和肾脏中的显著摄取。 脾。干扰素-α单独介导的放射性标记牛的掺入很少 当与IL-2联合使用时，IL-2的减少导致 在第4天可见细胞增殖。类似的IL-2抑制诱导 肺、肾、脾组织有明显的增殖现象。相比之下， 在第7天或第8天，干扰素-α+组获得了更高的放射性标记摄取率 IL-2处理小鼠肺、肝、肾与脏器的比较 单独使用IL-2或单独使用干扰素-α。干扰素-α对IL-2诱导的影响 细胞增殖呈剂量依赖性。细胞的持续增殖是 IL-2加干扰素-α注射9周后在大多数器官中观察到 连续几天。小鼠500rad大剂量预照射 消除了对IL-2和干扰素-α+的增殖反应 IL-2在第3天和第7天。接受细胞因子的肺的组织学研究 第3天和第7天的治疗证实了L25-IUdR的结果 参入试验。这些研究表明，体内的干扰素-α相互作用 以复杂的方式使用IL-2，并延长干扰素-α和 IL-2增加组织中淋巴样细胞的渗透可能起到一定作用 在抗肿瘤效应功能方面。最初的手稿正在印刷中。 癌症研究中心。

To understand the mechanism of synergistic anti-tumor effects, we have examined lymphoid cell proliferation in-vivo in various organs of mice in response to IL-2 and IFN-alpha administration. We have utilized a technique for labeling newly synthesized DNA in-vivo with 125-IUdR to examine proliferation of endogenous cells. After 4 days of IL-2 administration, a significant uptake of 125-IUdR was observed in the lungs, liver, kidneys an spleen. IFN-alpha alone mediated very little incorporation of radiolabel bu when administered in combination with IL-2, a reduction of IL-2 induced proliferation was seen on day 4. Similar inhibition of IL-2 induced proliferation was observed in the lungs, kidneys and spleen. In contrast, on days 7 or 8, higher uptake of radiolabel was obtained in IFN-alpha plus IL-2 treated lungs, liver and kidneys compared to organs of mice treated with IL-2 alone or IFN-alpha alone. The effects of IFN-alpha on IL-2 induce proliferation was dose dependent. Continued proliferation of cells was observed in most organs when IL-2 plus IFN-alpha was injected for 9 consecutive days. Pretreatment irradiation of mice at 500 rad largely eliminated the proliferative response to IL-2 as well as to IFN-alpha plus IL-2 at both days 3 and 7. Histological studies of lungs receiving cytokine therapy for days 3 and 7 corroborated the results of the l25-IUdR incorporation assay. These studies indicate that in-vivo IFN-alpha interact with IL-2 in a complex manner and prolonged treatment with IFN-alpha and IL-2 increases tissue infiltration of lymphoid cells that may play a role in antitumor effector functions. The initial manuscript is in press in the Cancer Research.