Influence of interleukin-3 (IL-3) on the hematopoietic toxicity associated with combination anti-viral drugs (zidovudine and DDI) in vitro using retrovirus-infected bone marrow cells.
The drug zidovudine (AZT), a synthetic thymidine analog, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has been associated with the development of hematopoietic toxicity manifested by anemia, neutropenia, and on occasion thrombocytopenia. This toxicity has resulted in the development of alternative dideoxynucleoside drugs capable of exerting anti-viral potency while minimizing the risk for inducing organ toxicities. One such dideoxynucleoside drug is 2',3'-dideoxyinosine (ddI). Clinical trials are currently evaluating the effect of combination anti-viral drug treatment such as zidovudine plus ddI. We report here the results of studies designed to evaluate the effect of interleukin-3 (IL-3) on its ability to influence the hematopoietic toxicity associated with zidovudine and ddI following combination with retroviral-infected murine bone marrow cells. Toxicity was evaluated by quantitating several classes of hematopoietic progenitor stem cells such as granulocyte-macrophage (CFU-GM), erythroid (CFU-E and BFU-E) and megakaryocyte (CFU-Meg). Dose-escalation IL-3 provided protection of anti-viral drug induced suppression of progenitor cells when combined in the presence of the ID50 concentration of either zidovudine or ddI; however, when zidovudine and ddI were combined, IL-3 was less effective in providing protection against drug-induced toxicity at any concentration examined. These results indicate that IL-3 is effective in reducing anti-viral drug-induced hematopoietic toxicity associated with single-agent use; however, IL-3 is less effective when such drugs are used in combination.
Gallicchio
V S
VS
Department of Medicine, Lucille P. Markey Cancer Center, Lexington, Kentucky.
Hughes
N K
NK
D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000382:microbiology; D001854:Bone Marrow Cells; D016049:Didanosine / Q000633:toxicity; D004347:Drug Interactions; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007075:Immunoglobulin M / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000503:physiopathology*; D013234:Stem Cells / Q000187:drug effects; D015215:Zidovudine / Q000633:toxicity
D000998:Antiviral Agents; D007075:Immunoglobulin M; D007377:Interleukin-3; D015215:Zidovudine; D016049:Didanosine