In vitro activity on myeloid progenitors of a combination of 2-chloro-2'-deoxyadenosine and interferon alpha: the effects of IL-1 and GM-CSF.

The toxic effects of a combination of 2-chloro-2'-deoxyadenosine (CDA) and interferon alpha (IFN-alpha), with and without addition of interleukin 1 (IL-1) and/or granulocyte macrophage colony stimulating factor (GM-CSF), on the in vitro growth of peripheral blood granulocyte macrophage committed progenitors (CFU-GM) from 10 normal subjects were investigated. CDA concentration ranged from 15.6 nmol/l to 1 mumol/l, IFN-alpha sole concentration was 10 IU/ml. IL-1 and/or GM-CSF were added at concentrations of 2000 pg/ml and 10 ng/ml, respectively. CDA induced a dose dependent inhibitory effect on CFU-GM growth. Addition of IFN-alpha increased CFU-GM inhibition induced by CDA only at lower concentrations of the latter. IL-1 and GM-CSF, separately or in combination, did not counteract the inhibitory activity of the CDA-IFN-alpha combination.