Effect of arsenic trioxide on cytokine expression by acute promyelocytic leukemia cells.
OBJECTIVE
To detect the expression of cytokines by acute promyelocytic leukemia (APL) cells before and after exposure to arsenic trioxide.


METHODS
Diagnoses were performed according to the FAB cytological classification criteria and cytogenetic criteria. Bone marrow or blood samples from APL patients were collected in heparinized tubes, then primary APL cells were separated by traditional Ficoll-Hypaque density centrifugation and purified after adherence to plastic surfaces. IL-1(beta), IL-6, IL-8, TNF alpha and G-CSF levels in the leukemia cell culture supernatants were detected by ELISA. At the same time, nitro blue tetrazolium (NBT) reduction test was used to detect the differentiation of APL cells.


RESULTS
After 96 hours exposure to arsenic trioxide, 10 - 6 mol/L in vitro or 10 mg/d in vivo, APL cells showed a significant increase of IL-1(beta) (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 alpha when compared with 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-1(beta) secretion ratio or G-CSF secretion ratio. The cell number ratio in patients with detectable IL-1(beta) or G-CSF was higher than that without detectable IL-1(beta) or G-CSF.


CONCLUSIONS
IL-1(beta) and G-CSF secretion may play an important role in the proliferation of APL cells after exposure to arsenic trioxide.
Jiang
Guosheng
G
Department of Hemato-oncology, Shandong Academy of Medical Science, Shandong University, Jinan 250062, China. Jianggsh@sohu.com
Bi
Kehong
K
Tang
Tianhua
T
Zhang
Yukun
Y
Ren
Haiquan
H
Jiang
Fengqin
F
Ren
Qinghua
Q
Zhen
Gang
G
Liu
Chuanfang
C
Peng
Jun
J
Guo
Guiyue
G
Liu
Xiulan
X
Tian
Zhigang
Z
D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001152:Arsenicals; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D010087:Oxides; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D000077237:Arsenic Trioxide