三氧化二砷对急性早幼粒细胞白血病细胞分泌细胞因子的影响与意义

为了探讨细胞因子在三氧化二砷诱发APL细胞白细胞升高的作用 ,首先按照FAB细胞形态学和细胞遗传学标准选择APL患者。常规Ficoll密度梯度法分离骨髓和PBMC ,体外培养 1h去除贴壁细胞。体外IL 1β、IL 6、IL 8、TNF α和G CSF分泌水平采用ELISA方法进行测定 ,NBT还原实验用以检测APL细胞分化状态。直接细胞计数法和MTT法观察细胞增殖变化。研究结果证实体外 10 6M或体内以 10mg/d三氧化二砷治疗 96h后 ,APL细胞分泌IL 1β和G CSF平均水平升高 (P <0 0 5 ) ,IL 6和IL 8水平降低 (P <0 0 5 ) ,TNF α水平无明显变化 (P >0 0 5 )。进一步分析结果表明 ,体外APL细胞的增值比率与IL 1β或G CSF分泌升高比率呈现正相关 ,检测到IL 1β或G CSF患者的细胞数量增加比率高于未检测到IL 1β或G CSF组 ,说明IL 1β或G CSF分泌增加在三氧化二砷诱导后的APL细胞增殖中起着一定作用

Variation of Cytokines in Patients with Acute Promyelocytic Leukemia after Exposure to Arsenic Trioxide

To detect the modulation of production of hematopoietic growth factors of acute promyelocytic leukemia (APL) cells after incubation with exposure to arsenic trioxide,and elucidate whether cytokine secretion was contributed to the proliferation of APL cells,primary APL cells from de novo cases with APL,which were diagnosed according to the FAB cytological classification criteria and cytogenetic criteria,were separated and purified by traditional Ficoll Hypaque density centrifugation and enriched after adherence to plastic surfaces IL 1β,IL 6,IL 8,TNF α and G CSF levels in the leukemia cell culture supernatants were estimated by ELISA method NBT reduction test was used to detect the differentiation of APL cells The cell number count and MTT method was used to measure the proliferation of APL cells The results showed that after 96 h exposure to arsenic trioxide 10 6 M in vitro or treatment with 10 mg/day in vivo,APL cells showed a significant increase of IL 1β ( P <0 05) and G CSF ( P <0 05) production,and a significant decrease of IL 6 ( P <0 05) and IL 8 ( P <0 05),however,there was no obvious variation of TNF α,if compared with that of APL cells without exposure to arsenic trioxide On the other hand,the proliferation ratio of APL cells in vitro was statistically correlated to the IL 1β secretion ratio or G CSF secretion ratio And the cell number ratio in patients with detectable IL 1β or G CSF was higher than that without detectable IL 1β or G CSF These results indicated that IL 1β and G CSF secretion play an important role in the proliferation of APL cells after exposure to arsenic trioxide