INFLUENCE OF INTERLEUKIN-3 ON ZIDOVUDINE (AZT)-INDUCED INVITRO TOXICITY TO HUMAN HEMATOPOIETIC PROGENITORS

Zidovudine (AZT), the antiviral drug used in the treatment of acquired immunodeficiency syndrome (AIDS), produces some toxicity to the hematopoietic system. Although several hematopoietic growth factors are currently undergoing clinical trials to evaluate their ability to modulate antiviral toxicity, there are scant data which support their ability to ameliorate AZT toxicity on hematopoietic progenitor cells when combined in vitro. We describe in this report the results of studies designed to evaluate in vitro the capacity of the cytokine interleukin-3 (IL-3), in dose-escalation fashion, to modulate AZT toxicity on normal human marrow derived granulocyte/erythroid/macrophage/megakaryocyte colony-forming units (CFU-GEMM), CFU-granulocyte/macrophage (CFU-GM) and erythroid burst-forming units (BFU-E). Colony formation for each progenitor was increased in the presence of IL-3 compared to cultures plated in its absence. In the presence of AZT (ID50 dose, used for each progenitor), IL-3 reduced AZT toxicity, with the most significant response observed for CFU-GEMM, indicating IL-3 may exert an effect on early, less differentiated hematopoietic progenitors. These studies indicate IL-3 may be an effective agent in reversing the hematopoietic toxicity associated with AZT; however, further in vivo studies are required before clinical use of IL-3 is advocated.