Influence of human recombinant interferon-alpha and interferon-gamma on bone marrow progenitor cells of HIV-positive individuals.
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-alpha (IFN-alpha) and IFN-gamma, 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-alpha and IFN-gamma 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-alpha 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-alpha for CFU-GM growth was 1095.8 U/ml and above 3000 U/ml. When IFN-gamma 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 (greater than 3000 U/ml). The ID50 for CFU-GEMM was below the lowest dose levels of IFN alpha and IFN gamma tested in both groups (less than 10 U/ml). The inhibitory effects could be specifically neutralized by monoclonal antibodies against IFN-alpha and IFN-gamma, thus confirming that the suppressive effects were due to the cytokines used.
Geissler
R G
RG
University of Frankfurt/Main, Department of Hematology, Germany.
Ottmann
O G
OG
Kojouharoff
G
G
Reutzel
P
P
Eder
M
M
Hoelzer
D
D
Ganser
A
A
D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D002478:Cells, Cultured; D015483:HIV Antibodies / Q000276:immunology; D006679:HIV Seropositivity / Q000473:pathology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology / Q000502:physiology
D015483:HIV Antibodies; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007371:Interferon-gamma