Effect of interleukin 1 and PTH related protein on hypercalcemia in adult T-cell leukemia

我们研究了为什么高钙血症经常与成人T细胞白血病相关。成人T细胞白血病（ATL）细胞及其细胞系MT 2细胞的生长通过向培养基中添加钙以剂量依赖性方式被促进。在4 mM钙时诱导最大反应，其异常地高于正常钙水平2.5mM。在与上述相同的条件下，已知为强骨吸收刺激因子（BRSF）的白细胞介素1（IL 1）的产生和IL 1受体的表达也相当增强。这些结果表明在ATL的高钙血症中存在涉及IL 1的自分泌机制。也就是说，ATL细胞产生的IL 1刺激骨吸收并诱导高钙血症，这增强了ATL细胞的生长，我们还发现，在恶性肿瘤体液性高钙血症（HHM）中最重要的BRSF是PTH相关蛋白（PTHRP）的mRNA，通过北方印迹杂交分析，在ATL细胞中表达，并且C-结果表明，ATL合并高钙血症患者血清和尿液中PTHrP片段均明显增高，提示ATL高钙血症的发生可能是由于IL 1的自分泌机制与ATL细胞PTHRP的产生协同作用所致。

We studied about the reason why hypercalcemia is very frequently associated with adult T-cell Leukemia. The growth of adult T-cell leukemia(ATL)cells and its cell line, MT2 cells were enhanced by addition of calcium to the media in a dose dependent manner. The maximum response was induced at 4 mM calcium, which was abnormally higher than that of the normal calcium level, 2.5 mM. The production of interleukin 1(ILl), which is known to be strong bone resorption stimulating factor(BRSF), and the expression of ILl receptor was also rather enhanced in the same condition as mentioned above. These results suggest the presence of autocrine mechanism involving ILl in hypercalcemia in ATL. Namely, ILl produced by ATL cells stimulate bone resorption and induce hypercalcemia, which enhance the growth of ATL cells, ILl production and ILl receptor expression followed by higher hypercalcemia in ATL.We also recognized that mRNA of PTH-related protein(PTHRP)which is most important BRSF in humoral hypercaleemia of malignancy(HHM)was expressed in ATL cells by northern blot hybridization assay and that C-fragment of PTHrP assayed by using RIA was increased in serum and urine of patients with ATL associated with hypercalcemia.In conclusion, it is suggested that very high degree of complication of hypercalcemia in ATL may be induced by synergetic effect of ILl production through a kind of autocrine mechanism and PTHRP production from ATL cells.