Cytokine secretion in patients with acute promyelocytic leukemia after treatment with all-trans retinoic acid

Abstract

Objective: To detect the modulation of cytokines production by acute promyelocytic leukemia (APL) cells before or after exposure to all-trans retinoic acid (ATRA). 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 microfuge tube. Primary APL cells were separated and purified by traditional Ficoll-Hypaque density centrifugation and enriched after adherence to plastic surfaces. IL-1β, IL-6, IL-8, TNFα and G-CSF levels in the supernatants of cultured leukemia cells were estimated by ELISA method. NBT method was used to detect the differentiation of APL cells at the same time. Results: 96 h after exposure to ATRA at 10⁻⁶ M in vitro or 60 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 TNFα. On the other hand, the proliferation of APL cells in vitro was statistically correlated to the IL-1β secretion or G-CSF secretion. 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. Conclusion: IL-1β and G-CSF secretion may play an important role in the proliferation of APL cells after exposure to ATRA.