AZIDOTHYMIDINE AND INTERFERON-ALPHA IN-VITRO EFFECTS ON HEMATOPOIESIS- PROTECTIVE IN-VITRO ACTIVITY OF IL-1 AND GM-CSF

Preclinical and clinical studies with an azidothymidine (AZT)/interfer on-alpha (IFN-alpha) combination resulted in a marked and synergistic antiretroviral activity. The administration of the two drugs in HIV-se ropositive patients affected with Kaposi's sarcoma, however, induced n eutropenia, thrombocytopenia, and, in some cases, anemia. A possible m eans to improve the therapeutic index of AZT and/or IFN-alpha in AIDS patients could be the addition of hematopoietic growth factors. In vit ro activity of cytokines on the hematotoxicity of the AZT-IFN-alpha as sociation has not yet been studied. We have performed an in vitro stud y to evaluate the toxicity of AZT, IFN-alpha, or both on peripheral bl ood hematopoietic progenitors (CFU-GM and BFU-E) and to assess the act ivity of interleukin 1 (IL-1), granulocyte-macrophage colony-stimulati ng factor (GM-CSF), or both in modifying AZT-IFN-alpha hematotoxicity. Results indicate that AZT, IFN-alpha, and combinations of the two hav e a dose-dependent inhibitory effect;on the in vitro growth of periphe ral blood hematopoietic progenitors. Combinations of AZT and IFN-alpha inhibited CFU-GM and BFU-E proliferation in an additive manner. Neith er IL-1 nor GM-CSF alone was able to induce a significant reduction of AZT-induced damage. Only the addition to the cultures of both cytokin es partially curbed the antiproliferative activity of AZT at low dosag es.