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

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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.