In vitro effect of granulocyte-colony stimulating factor and all-trans retinoic acid on the expression of inflammatory cytokines and adhesion molecules in acute promyelocytic leukemic cells

Differentiation therapy with all-trans retinoic acid (ATRA) represents a la ndmark approach in the treatment of acute promyelocytic leukemia (APL). How ever, a potentially fatal complication of retinoic acid (RA) syndrome occur s in about a quarter of patients and its pathophysiology is still unclear. In order to investigate whether or not the treatment with ATRA leads to inc reased elaboration of inflammatory cytokines and adhesion molecules by the APL cells, the expression of interleukin (IL)Ip, tumor necrosis factor (TNF )-alpha, IL-8, L-selectin and intercellular adhesion molecule-1 (ICAM-1) wa s examined in the APL cells after induction of differentiation with ATRA in the presence or absence of granulocyte-colony stimulating factor (G-CSF) o r IL-3 in the present study. Cytokine elaboration by the treated cells was detected using both Northern blotting and enzyme-linked immunosorbent assay . Our results have shown that ATRA induces an increased expression of IL-8, IL-1 beta, TNF-alpha and ICAM-1 in APL cells, which can be amplified by th e addition of G-CSF. These data imply that the induction of inflammatory cy tokines in APL cells may play an important role in the pathogenesis of RA s yndrome. Furthermore, G-CSF, through its potent differentiating activity, m ay increase the risk of such complications during ATRA treatment.