Inhibition of human immunodeficiency virus type 1 multiplication by transforming growth factor beta 1 and AZT in HIV-1-infected myeloid cells. 1995

V McKiel, and Z Gu, and M A Wainberg, and J Hiscott
Lady Davis Institute for Medical Research, Jewish General Hospital, Department of Microbiology and Immunology, Montreal, Quebec, Canada.

Myeloid cells are important reservoirs of HIV-1 infection. In response to pathogenic agents, macrophages secrete inflammatory cytokines that can modulate viral replication and contribute to AIDS pathogenesis. Because HIV replication is dependent on cellular activation, immunosuppressive cytokines that deactivate macrophages and T cells may be important modulators of an antiviral effect. We tested the anti-HIV potential of the immunosuppressive cytokine-transforming growth factor beta (TGF-beta 1) alone and in combination with AZT in a new monomyeloblastic model of HIV-1 infection. The PLB-985 cell model was infected with HIV IIIB strain, and the course of HIV-1 infection and replication was monitored by reverse transcriptase assay, p24 immunofluorescence, and northern blot analysis of HIV-1-specific mRNA. TGF-beta 1 as a single agent had no effect on the multiplication of HIV-IIIB in de novo-infected PLB 985 monomyeloblastic cells. However, cotreatment with TGF-beta 1 and AZT synergistically slowed virus multiplication within the first week following infection, as determined by reverse transcriptase measurement, p24 antigen detection, and northern blot analysis of viral RNA. The synergistic actions of TGF-beta 1 and AZT were also observed in PLB 985 cells infected with an AZT-resistant strain of HIV-1 (HIV 1393). Synergism between nucleoside analogs and cytokines may be an important therapeutic approach to HIV-1 infection. Elucidation of the role of cytokines in controlling the degree of HIV multiplication may have an impact on both clinical treatments and understanding the progression to AIDS.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D015479 Leukemia, Myelomonocytic, Acute A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin. Leukemia, Myeloid, Acute, M4,Leukemia, Myeloid, Naegeli-Type,Myeloid Leukemia, Acute, M4,Myeloid Leukemia, Naegeli-Type,Myelomonocytic Leukemia, Acute,Acute Myelomonocytic Leukemia,Acute Myelomonocytic Leukemias,Leukemia, Acute Myelomonocytic,Leukemia, Naegeli-Type Myeloid,Leukemias, Acute Myelomonocytic,Myeloid Leukemia, Naegeli Type,Myelomonocytic Leukemias, Acute,Naegeli-Type Myeloid Leukemia

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