Abstract
Zidovudine, the antiviral drug used in the treatment of acquired immunodeficiency syndrome (AIDS), causes toxicity to the haematopoietic system. Although use of the haematopoietic growth factors, GM-CSF and erythropoietin have been investigated in clinical trials to modulate antiviral toxicity, there is scant data which supports their ability to ameliorate zidovudine induced toxicity on haematopoietic progenitor cells when combined in vitro. We describe here the results of studies designed to evaluate the capacity of additional haematopoietic factors such as granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) to modulate zidovudine-induced toxicity on G-CSF and M-CSF dependent-colony formation in the presence or absence of zidovudine in vitro. These factors were also studied combined with erythropoietin in culture for the early erythroid progenitor BFU-E using adherent, T-cell, depleted normal human bone marrow cells in the presence or absence of zidovudine. In the presence of zidovudine at the concentration producing 50% inhibition of G- and M-CSF dependent colony formation, (5 × 10−5M), dose-escalation of either G-CSF or M-CSF failed to ameliorate zidovudine toxicity. However, in the presence of zidovudine at the concentration that produces 50% inhibition of BFU-E (5 × 10−9M), and optimal erythropoietin (1 unit ml−1), G-CSF ameliorated zidovudine inhibition of BFU-E, which was not observed with M-CSF. In the presence of erythropoietin, G-CSF increased significantly normal BFU-E. These studies indicate that G-CSF may be useful in ameliorating zidovudine-induced anaemia and suggest G-CSF may act as a synergistic factor to enhance erythropoietin to support the growth of erythroid progenitors in conditions where erythropoitin is ineffective.