Effect of azacytidine in the release of leukemia inhibitory factor, oncostatin m, interleukin (IL)-6, and IL-11 by mononuclear cells of patients with refractory anemia.
5-azacytidine (AZA) yields hematologic improvement in patients with myelodysplastic syndromes (MDS). Ineffective hemopoiesis in MDS produce the paradox of high intramedullary cellularity with peripheral cytopenias. Leukemia inhibitory factor (LIF), oncostatin M (OSM), interleukin (IL)-6, and IL-11 regulate hemopoiesis and LIF, OSM, and IL-6 also inhibit the proliferation of myeloid leukemic cell lines through the signal-transducing subunit gp130. These IL-6-type cytokines were measured by enzyme-linked immunosorbent assay in cell culture supernatants (SN) obtained from peripheral blood mononuclear cells (MNC) and monocyte-depleted MNC of patients with refractory anemia (RA; n=12) and healthy individuals (n=10). AZA down-regulated OSM, IL-6, and IL-11 release by MNC of patients but not by MNC from healthy individuals. Patient's SN had significantly lower concentrations of LIF, OSM, and IL-11 than SN of normal subjects. When monocyte-depleted MNC of patients were stimulated with phytohemagglutinin a significant increment in OSM levels was observed. In contrast, monocyte depletion in healthy subjects did not cause any significant change in OSM values. We conclude that: (a) AZA inhibits the release of OSM, IL-6, and IL-11 exclusively in RA-diseased MNC, (b) Patient's MNC release subnormal amounts of LIF, OSM, and IL-11, and (c) RA-derived monocytes probably down-regulate OSM release by phytohemagglutinin-activated MNC.
López-Karpovitch
Xavier
X
Hematology and Oncology Department, Laboratory of Cell Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan 14000, México, DF, México. xlopezk@quetzal.innsz.mx
Barrales-Benítez
Olga
O
Flores
Martín
M
Piedras
Josefa
J
D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000097:blood* / Q000188:drug therapy; D000963:Antimetabolites / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology*; D002478:Cells, Cultured / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology
D000963:Antimetabolites; D017077:Culture Media, Conditioned; D006131:Growth Inhibitors; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D010835:Phytohemagglutinins; D053683:Oncostatin M; D001374:Azacitidine