Production of interleukin 6, leukemia inhibitory factor and granulocyte-macrophage colony stimulating factor by peripheral blood mononuclear cells in fanconi's anemia

The aim of this study was to test the in vitro cytokine production by peripheral blood mononuclear cells (PBMCs) in patients with Fanconi's anemia (FA). Phytohemagglutinin (PHA)-stimulated PBMCs from 21 patients with FA were studied for their ability to produce interleukin 6 (IL-6), leukemia inhibitory factor (LIF) and granulocyte-macrophage colony stimulating factor (GM-CSF). Enzymatic immunoassay (EIA) was used for both IL-6 and LIF, while GM-CSF was evaluated in a highly sensitive biological assay provided by GM-CSF-dependent M-07e cells. A significant decrease of IL-6 was detected in 9 out of 11 FA patients compared with five normal donors, while similar amounts of LIF were produced from 21 FA patients and 21 healthy subjects. A drastic increase of active GM-CSF was documented in PHA-stimulated PBMC-conditioned medium in all 18 FA patients tested. Since IL-6 and GM-CSF play an important role in maintaining basal hemopoiesis, our results suggest that an abnormal cytokine network may be involved in the pathogenesis of FA pancytopenia.