重组人IL－6对大鼠急性白血病细胞体外增殖的抑制

我们已报道重组大鼠ＩＬ－３和小鼠ＧＭ－ＣｓＦ对ＬＴ１２白血病细胞的增殖有不同程度的抑制活性。本研究发现重组人ＩＬ－６在１０００～５０００Ｕ／ｍｌ呈剂量依赖性抑制ＬＴＩ２白血病祖细胞集落形成及ＤＮＡ合成。５０００Ｕ／ｍｌ对ＣＦＵ－Ｌ的抑制率达５２．９％，而对ＤＮＡ合成则为４１．３％，此外，ＩＬ－６还明显增加ＩＬ－３和ＧＭ－ＣＳＦ对ＬＴ１２细胞的抑制活性，对ＣＦＵ－Ｌ的抑制强弱依次为ＩＬ－６＋ＧＭ－ＣＳＦ、ＩＬ－３＋ＧＭ－ＣＳＦ、及ＩＬ－６＋ＩＬ－３，ＩＬ－６＋ＩＬ－３＋ＧＭ－ＣＳＦ三因子的结合并不能增加抑制效应；对ＤＮＡ合成的抑制作用为ＩＬ－６＋ＩＬ－３＋ＧＭ－ＣＳＦ＞ＩＬ－６＋ＧＭ－ＣＳＦ＞ＩＬ－３＋ＧＭ－ＣＳＦ＞ＩＬ－６＋ＩＬ－３。提示上述造血因子除刺激正常造血外，在白血病的治疗中可能具有一定意义。

Suppressive effects of recombinant human interlcuhn-6 on the in uitro proliferation of acute leukemic cells in rat

The suppressive activities of recombinant rat interleukin-3(IL3)and murinegranulocyte-macrophage colony stimulating factor(GM-CSF)on the proliferation of LT12leukenllc eells was reported.In this study,recombinant human interleukin-6(IL6)was as-sessed for its regulating effects on leukemo poiesis in the presenee or absenee of IL3 andGM-CSF using LT12 eell line,a subline of BNML rat model.This model was generally ac-cepted as one of the most realistic model for human acute myelocytic leukenlla due to itsclinical relevanee. In agreement with our p reliminary study,when acting alone IL6 exertedquite suppressive activity against LT12 eells both in leukemic blast colony formation andDNA synthesis.Suppression was clearly evident only at higher concentration of 4000U/mland 5000U/ml which resulted in morethan 50% reduction in colony numbers.When DNA synthesisin LT12 eells was also inhibited supporting the conclusion that this is a genuine property ofIL6.More strikingly,IL6 showed enhaneed effects on suppressive activity of IL3 andGM-CSF on the proliferation of LT12 eells.It is evident that IL6 plus GM-CSF was themost potent combination used which always gave a maximum suppression in all ofcombination of factors in CFU-L assay,and the combination of IL6 IL3 GM-CSF inDNA synthesis.Coupled with its stimulation of proliferation effects on nomalhelnatopoiesis,IL6 alone or in combination with IL3 and GM-CSF may have a therapeuticalpotential in the treatment of some acute myelocytic leukemias.