Effects of recombinant human cytokines on cytarabine activity in K562 human myeloid leukaemia cells.
The K562 cell line provides a unique population of primitive human myeloid leukaemia cells which can be induced to differentiate along the erythroid, granulocytic, macrophage and megakaryocytic lineages in response to several agents. Cytarabine is not only the most widely used drug in the treatment of myeloid leukaemia but also the most effective agent in K562 cells. The effects of five recombinant human cytokines - interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha, interferon-beta and interferon-gamma on cytarabine-induced growth inhibition and differentiation of K562 cells was studied in liquid suspension cultures. GM-CSF and to a lesser extent IL-3 enhanced the antiproliferative effect of cytarabine in K562 cells, whereas the three interferons reduced it. The efficacy of cytarabine in inhibiting the growth of K562 cells was doubled by its combination with GM-CSF or IL-3 but was halved by its combination with interferons. The five cytokines did not significantly affect cytarabine-induced erythroid differentiation of K562 cells. The present results appear to favour the use of GM-CSF and IL-3 but not of interferons in future treatment strategies based on a combined cytokine and chemotherapy approach for myeloid leukaemia.
Hassan
H T
HT
Leukämie-Forschung, Institut für Pharmazie, Freie Universität Berlin, FRG.
Maurer
H R
HR
D003561:Cytarabine / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004347:Drug Interactions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D016207:Cytokines; D007370:Interferon Type I; D007377:Interleukin-3; D011994:Recombinant Proteins; D003561:Cytarabine; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor