EFFECTIVE MODULATION OF THE HEMATOPOIETIC TOXICITY ASSOCIATED WITH ZIDOVUDINE EXPOSURE TO MURINE AND HUMAN HEMATOPOIETIC PROGENITOR STEM-CELLS INVITRO WITH LITHIUM-CHLORIDE

The drug zidovudine (AZT), a synthetic thymidine analogue, has been us ed in the treatment of acquired immunodeficiency syndrome (AIDS). Clin ical use of zidovudine has induced haematopoietic toxicity manifested by anaemia, neutropenia, frequent thrombocytopenia. and overall bone-m arrow suppression. The monovalent cation lithium has been shown to be an effective agent capable of modulating several aspects of haematopoi esis such as the induction of neutrophilia. thrombopoiesis, and protec tion against suppression of haematopoietic progenitor stem cells follo wing exposure to anticancer drugs and/or radiation in the treatment of malignant disease. We here report the results of studies designed to evaluate the effectiveness of lithium in reversing and/or protecting a gainst either murine or human bone marrow derived haematopoietic proge nitors, i.e. (CFU-GM, CFU-Meg, and BFU-E) when co-cultured in the pres ence of zidovudine in vitro. Lithium chloride (LiCl) reversed zidovudi ne toxicity to either murine or human derived CFU-GM and CFU-Meg that was optimal at a concentration of 1 mm (P < 0.05). However, the additi on of lithium failed to influence zidovudine toxicity toward either mu rine or human BFU-E. In summary. these results support the scant clini cal studies that have described the presence of neutrophilia and/or th rombopoiesis in zidovudine-treated AIDS patients receiving lithium. In addition, these data further confirm the need for more detailed evalu ation of lithium as an adjuvant agent to reduce the haematopoietic tox icity associated with the use of antiviral therapy in HIV-infected pat ients.