Hemopoietin-1 activity of interleukin-1 (IL-1) on acute myeloid leukemia colony-forming cells (AML-CFU) in vitro: IL-1 induces production of tumor necrosis factor-alpha which synergizes with IL-3 or granulocyte-macrophage colony-stimulating factor
Delwel, R.; van Buitenen, C.; Salem, M.; Oosterom, R.; Touw, I.; Löwenberg, B.
Leukemia 4(8): 557-560
1990
ISSN/ISBN: 0887-6924
PMID: 2201834
Accession: 007393541
Interleukin-1 (IL-1) has hemopoietin-1 (H-1) activity, i.e., it synergizes with macrophage-colony stimulating factor (M-CSF), granulocyte-macrophages-CSF (GM-CSF) and interleukin-3 (IL-3) in stimulating in vitro colony formation of hematopoietic progenitor cells. In this study the synergistic activity of IL-1 was investigated on IL-3 and GM-CSF induced growth of acute myeloid leukemia colony forming cells (AML-CFU) in vitro. Among 12 cases of human AML, IL-1 significantly elevated IL-3 stimulated colony numbers in eight instances and enhanced GM-CSF induced colony growth in five cases. As IL-I is an inducer of cytokine production and since tumor necrosis factor (TNF) elevates IL-3 or GM-CSF induced proliferation of AML-CFU, we examined whether IL-1 enhanced AML-CFU growth via the induction of TNF production. Neutralizing anti-TNF-.alpha. antibodies significantly decreased IL-1/IL-3 or IL-1/GM-CSF stimulated colony numbers in six of seven cases studied, whereas anti-TNF-.beta. had no effect, indicating that endogenously produced TNF-.alpha. costimulated the growth of AML-CFU. Furthermore, AML blast cells stimulated by IL-1 released increased amounts of TNF-.alpha. (between 25 and 533 pg/ml; median 255 pg/ml) into the culture medium (TNF-.alpha. specific radioimmunoassay) as compared with noninduced AML cells (< 1 to 149 pg TNF-.alpha./ml; median 31 pg/ml). Thus, the effect of IL-1 on AML-CFU proliferation is not the result of direct activation of AML progenitors, but IL-1 stimulates the release of TNF-.alpha. by AML cells and endogenous TNF subsequently synergizes with IL-3 or GM-CSF.