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

• Published in: Cytokine (Philadelphia, Pa.) Vol. 20; no. 4; pp. 154 - 162
• Main Authors: López-Karpovitch, Xavier, Barrales-Benı́tez, Olga, Flores, Martı́n, Piedras, Josefa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 24.11.2002
• Subjects: Adult; Aged; Anemia, Refractory - blood; Anemia, Refractory - drug therapy; Antimetabolites - pharmacology; Azacitidine - pharmacology; Cells, Cultured - secretion; Culture Media, Conditioned - chemistry; Enzyme-Linked Immunosorbent Assay; Female; Growth Inhibitors - secretion; Humans; Interleukin-11 - secretion; Interleukin-6 - secretion; Leukemia Inhibitory Factor; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - secretion; Lymphokines - secretion; Male; Middle Aged; myelodysplastic syndromes/5-azacytidine/leukemia inhibitory factor/oncostatin M/interleukin-6-type cytokines; Oncostatin M; Peptides - secretion; Phytohemagglutinins - pharmacology; myelodysplastic syndromes/5-azacytidine/leukemia inhibitory factor/oncostatin M/interleukin-6-type cytokines
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2002.1998

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.