In vitro effects of IL-12 and IL-2 on NK cells, cytokine release and clonogenic activity in myelodysplastic syndromes (MDS)

• Published in: Leukemia Vol. 11; no. 10; pp. 1726 - 1731
• Main Authors: SARINA, B, CORTELEZZI, A, CATTANEO, C, POMATI, M, SILVESTRIS, I, DI STEFANO, M, LAMBERTENGHI-DELILIERS, D, HU, C, MONZA, M, MAIOLO, A. T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-10-1997; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blood cells; Bone marrow; Bone Marrow - drug effects; Bone Marrow Cells; CD3 antigen; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Division - drug effects; Cell Division - physiology; Cytokines; Cytokines - secretion; Female; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; Interferon; Interleukin 12; Interleukin 2; Interleukin-12 - pharmacology; Interleukin-2 - pharmacology; Killer Cells, Natural - drug effects; Killer Cells, Natural - physiology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes (mononuclear); Lymphocytes; Lymphocytes - drug effects; Lymphocytes - physiology; Male; Medical sciences; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - blood; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - pathology; Natural killer cells; Patients; Peripheral blood mononuclear cells; Phenotype; Tumor necrosis factor; Natural killer cell; Human; Interleukin 2; Cytokine; Interleukin 12; Biological effect; In vitro; Myelodysplastic syndrome; Colony forming cell
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2400813

We evaluated the in vitro effects of IL-12, alone and in association with IL-2 on MDS bone marrow and peripheral blood cells. Thirty-six patients and 14 healthy subjects were studied. Natural killer-activity (NK-a) levels and lymphocyte immunophenotypes were determined in fresh bone marrow (BMMNC) and peripheral blood mononuclear cells (PBMNC), which then were resuspended in medium containing IL-2, IL-12 or IL-2 + IL-12 for 7 days. Re-evaluation of NK-a levels, lymphocyte immunophenotypes, clonogenic activity and cytokine release showed that, unlike IL-2, IL-12 did not significantly increase NK-a or CD3-/56+ cell levels in either bone marrow or peripheral blood; IL-2 + 12 led to a significant increase that fell between the values reached by each cytokine alone. IL-2 + 12 and, although to a lesser extent, also IL-12 alone induced the release of large amounts of gamma-IFN and alpha-TNF. In addition, the number of clusters particularly decreased in the samples treated with IL-2 + 12 and IL-12 alone. Clonogenic activity was not modified after stimulation with any of the treatment. These data suggest that IL-12 induces the release of inhibitory cytokines in normal as well as MDS cells and that it could be used in patients with elevated bone marrow blastosis.