Influence of Human Recombinant Interferon-Alpha and Interferon-Gamma on Bone Marrow Progenitor Cells of HIV-Positive Individuals

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Abstract
As a result of a pathophysiologically unexplainable bone marrow failure, most patients with progressive stages of human immunodeficiency virus (HIV) infection develop anemia, leukopenia, and thrombocytopenia. Besides the possibility of immune-mediated cytolysis or of direct viral infection of hemopoietic progenitor cells, the inhibitory influence of cytokines, for example interferon-α (IFN-α) and IFN-γ, on hemopoiesis of HIV-infected patients might be considered as one parameter that contributes to myelosuppression. Therefore, progenitor cells from the bone marrow of HIV+ and HIV- persons were exposed to increasing concentrations of recombinant human IFN-α and IFN-γ in methylcellulose assays. The colony formation of pluripotent (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells was inhibited by both interferons. The 50% inhibitory doses (ID50) of IFN-α were 125.6 U/mL and 131.5 U/mL for BFU-E from HIV-infected persons and normal controls, respectively; the corresponding ID50 of IFN-α for CFU-GM growth was 1095.8 U/ml and above 3000 U/ml. When IFN-γ was studied the ID50 was 341.7 and 2794.6 U/ml for BFU-E from HIV-infected and healthy individuals, respectively, while the ID50 for CFU-GM was above the highest dose levels in both groups (>3000 U/ml). The ID50 for CFU-GEMM was below the lowest dose levels of IFNα and IFN-γ tested in both groups (<10 U/ml). The inhibitory effects could be specifically neutralized by monoclonal antibodies against IFN-α and IFN-γ, thus confirming that the suppressive effects were due to the cytokines used.