Interleukin-6 and interleukin-1 enhancement of GM-CSF-dependent proliferation of haematopoietic progenitor cells in myelodysplastic syndromes.

Interleukin-1 (Il-1) and Interleukin-6 (Il-6) have been reported to enhance the growth factor dependent colony formation of normal primitive haematopoietic progenitor cells as well as of leukaemic blast-cell progenitors. We investigated the effects of Il-1 beta and Il-6 in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) on the in vitro colony formation of myeloid progenitors from 23 patients with a myelodysplastic syndrome (MDS). Neither Il-1 beta nor Il-6 were found to have colony stimulating activity on their own. In normal bone marrow cultures, either stimulated with optimal or suboptimal doses of GM-CSF, no enhancing or antagonistic effect of Il-6 or Il-1 beta was detected. In a majority of the MDS cases, however, an enhancing effect of Il-6 and Il-1 beta in combination with GM-CSF was observed (20/23 and 10/21 cases respectively). In three cases of the Il-6 and GM-CSF combination an antagonistic effect was observed as well as in four cases of the Il-1 beta and GM-CSF combination. A delayed addition of Il-6 to the cultures did not result in an abrogation of the effect, indicating that Il-6 is not required immediately at the initiation of the culture. These results indicate that costimulation with Il-6 or Il-1 beta is able to augment the GM-CSF activity on MDS myeloid progenitor cells.