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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells of macrophage lineage constitute the main cellular target of Human Immunodeficiency Virus type 1 (HIV-1). Replication of HIV-1 in monocyte/macrophages is generally augmented by factors promoting their differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a key regular of the differentiation of cells of macrophage lineage. The effects of GM-CSF on HIV-1 replication in vitro are still controversial. Most of the published studies suggest that GM-CSF upregulates HIV-1 expression in both primary cultured macrophages and promonocytic cell lines. There have also been reports demonstrating that GM-CSF does not affect HIV-1 replication in cells of macrophage lineage or that GM-CSF can actually suppress HIV-1 expression. In vivo, GM-CSF administrated to HIV-positive patients at any stage of disease, without any antiretroviral therapy, appears to increase HIV-1 activity. The possible mechanism by which GM-CSF might affect HIV-1 replication in macrophages remains unclear.
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PMID:Effect of GM-CSF on HIV-1 replication in monocytes/macrophages in vivo and in vitro: a review. 965 46

Assessing the functionality of T lymphocytes is important in determining progression rate in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), transplant rejection, and autoimmune disease. Activation of T-cells in response to antigen results in expression of cytokines and cytokine receptors, proliferation, and development of effector function. Multiplexed flow cytometric analyses were developed to measure cytokine receptor expression, internal cytokine expression, and cytokine secretion by activated T-cells in vitro. Receptor expression was determined by the binding of phycoerythrin-labeled cytokines. Internal cytokine was determined by intracellular labeling with anti-cytokine antibodies. Cytokine secretion was determined by a flow cytometry-based immunofluorescence assay. The assays could be multiplexed, measuring up to six cytokines simultaneously and measuring cellular receptor expression simultaneously with cytokine secretion. The immunoassays were sensitive in the femtomolar range, allowing determination of normal serum levels of cytokines (<100 fg/ml). Using granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion as a marker for activation, it was determined that at peak secretion (68 h post activation) an average of 1,150 molecules of GM-CSF were produced per cell per hour. Active infection with several viruses reduced the ability of T-cells to be activated. Activated T-cells (1 x 10(6)) normally produced 4-8 pg/ml/h GM-CSF after 20 h of activation, impaired T-function resulted in a decrease to the 0.2-2.0 pg/ml/h range.
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PMID:T-lymphocyte functionality assessed by analysis of cytokine receptor expression, intracellular cytokine expression, and femtomolar detection of cytokine secretion by quantitative flow cytometry. 977 87

We performed a literature search for all clinical studies reporting outcomes in patients with the acquired immunodeficiency syndrome (AIDS) receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for any indication. Safety outcomes included human immunodeficiency virus replication, immune status, and frequency of opportunistic infections and neoplasms. Data were synthesized qualitatively. We identified 22 studies (274 patients): 12 addressed AIDS neutropenia, 8 AIDS cancer therapy, and 2 opportunistic infections. Viral burden was assessed by serum p24Ag in 15 studies. Nine reported no change in levels, three net decreases, and three net increases. All studies showing net increases involved patients receiving GM-CSF without a concurrent antiretroviral. The CD4 counts were unchanged in 5 studies, increased in 3, and not reported in 14. The incidence of neoplasms or new opportunistic infections was low. The literature suggests no increased risk of viral replication or clinical deterioration in patients with AIDS who take GM-CSF concurrently with zidovudine.
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PMID:Safety of GM-CSF in patients with AIDS: a review of the literature. 985 29

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used successfully to enhance neutrophil recovery in patients with various malignancies undergoing standard or high dose chemotherapy, with or without autologous or allogeneic bone marrow transplantation support, and offer potential advantages in these settings in terms of reducing the total costs of healthcare and/or improving therapeutic outcomes. Clinical trials are now aimed at identifying which patients and which nonhaematological malignancies will respond best to colony-stimulating factor (CSF) support, and which of the 2 factors is the most appropriate in each setting. Two areas of considerable interest at present are the potential for chemotherapy dose optimisation and intensification with CSF therapy, and the use of CSFs to permit the harvest and reinfusion of peripheral blood progenitor cells as an alternative to autologous or allogeneic bone marrow transplantation. In the case of dose-intensified chemotherapy, costs of treatment increase but the gain may be an increase in survival rates or disease-free intervals. The potential of G-CSF and GM-CSF therapy in other conditions, notably haematological malignancies such as myelodysplasia and myeloid leukaemias, and AIDS, means that these agents are likely to make a significant impact on the treatment of a wide range of debilitating conditions in the future.
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PMID:Colony-stimulating factors. Present status and future potential. 1015 91

Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progressive loss of CD4(+) T cells observed in AIDS patients. Because dendritic cells (DC) play an important role in the immunopathogenesis of human immunodeficiency virus (HIV) disease, we studied the infection of DC by HHV-6 and coinfection of DC by HHV-6 and HIV. Purified immature DC (derived from adherent peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody staining, and presence of virus in culture supernatants. However, HHV-6-infected DC demonstrated neither cytopathic changes nor functional defects. Interestingly, HHV-6 markedly suppressed HIV replication and syncytium formation in coinfected DC cultures. This HHV-6-mediated anti-HIV effect was DC specific, occurred when HHV-6 was added either before or after HIV, and was not due to decreased surface expression or function of CD4, CXCR4, or CCR5. Conversely, HIV had no demonstrable effect on HHV-6 replication. These findings suggest that HHV-6 may protect DC from HIV-induced cytopathicity in AIDS patients. We also demonstrate that interactions between HIV and herpesviruses are complex and that the observable outcome of dual infection is dependent on the target cell type.
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PMID:Human herpesvirus 6 infects dendritic cells and suppresses human immunodeficiency virus type 1 replication in coinfected cultures. 1019 98

Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway, which play a role in host defense, and are synthesized by both monocytes (peripheral blood monocyte [PBM]) and neutrophils (PMN). Because 5-LO metabolism is reduced in alveolar macrophages and PMN from acquired immunodeficiency syndrome (AIDS) subjects, we investigated the synthesis of LT by PBM and PMN from these subjects. There was a reduction (74.2% +/- 8.8% of control) in LT synthesis in PBM from human immunodeficiency virus (HIV)-infected compared with normal subjects. Expression of 5-LO (51.2% +/- 8.8% of control), and 5-LO activating protein (FLAP) (48.5% +/- 8.0% of control) was reduced in parallel. We hypothesized that this reduction in LT synthetic capacity in PBM and PMN was due to reduced cytokine production by CD4 T cells, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). We treated 10 AIDS subjects with GM-CSF for 5 days. PBM 5-LO metabolism ex vivo was selectively increased after GM-CSF therapy and was associated with increased 5-LO and FLAP expression. PMN leukotriene B(4) (LTB(4)) synthesis was also augmented and associated with increased 5-LO, FLAP, and cytosolic phospholipase A(2) expression. In conclusion, as previously demonstrated for PMN, PBM from AIDS subjects also demonstrate reduced 5-LO metabolism. GM-CSF therapy reversed this defect in both PBM and PMN. In view of the role of LT in antimicrobial function, cytokine administration in AIDS may play a role as adjunct therapy for infections.
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PMID:Granulocyte-macrophage colony-stimulating factor upregulates reduced 5-lipoxygenase metabolism in peripheral blood monocytes and neutrophils in acquired immunodeficiency syndrome. 1057 6

The role of human immunodeficiency virus type 1 (HIV-1) infection on the ability of human monocytes/macrophages to phagocytose Mycobacterium avium complex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on this function were investigated. By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was found to impair the ability of monocyte-derived macrophages to phagocytose MAC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosis was not altered by exposure to a mutant form of GM-CSF (E21R) binding only to the alpha chain of the GM-CSF receptor, suggesting that signaling by GM-CSF that leads to augmentation of phagocytosis is via the beta chain of the receptor. In a patient with AIDS and disseminated multidrug-resistant MAC infection, GM-CSF treatment improved phagocytosis of MAC by peripheral blood monocytes and reduced bacteremia. These results imply that GM-CSF therapy may be useful in restoring antimycobacterial function by human monocytes/macrophages.
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PMID:Granulocyte-macrophage colony-stimulating factor augments phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type 1-infected monocytes/macrophages in vitro and in vivo. 1060 95

Oral recurrent aphthous ulceration (RAU) is a well-recognized complication in patients infected with human immunodeficiency virus. RAU can be progressive and destructive, causing dysphagia and secondary malnutrition. The aetiology of RAU remains unknown, and its response to available treatments is often unsatisfactory. We describe three patients with advanced AIDS who suffered from extensive RAU which failed to respond to several treatments, including topical viscous lidocaine and topical and systemic glucocorticoids. Owing to difficulties in using thalidomide (two patients had neurological conditions which precluded thalidomide use), all three patients were treated with an oral solution containing recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 400 microg in 5% glucose 200 mL). From the first application, all three patients showed significant improvement of their lesions and amelioration of pain, and they were completely cured in a few days. No adverse effects were recorded. The patients did not show relapses of RAU over a prolonged follow-up. Controlled trials are warranted in order to establish the role of GM-CSF as a valid, alternative option for aphthous ulcerations of the mouth in AIDS patients in whom corticosteroids or thalidomide are not suitable.
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PMID:Successful treatment of aphthous ulcerations in AIDS patients using topical granulocyte-macrophage colony-stimulating factor. 1065 17

The depletion of immune T cells by human immunodeficiency virus type-1 (HIV-1) infection is a major mechanism involved in the pathogenesis of AIDS. Here, we examined a possible effector function of blood monocyte-derived dendritic cells (DCs) to induce apoptosis in bystander CD4+ and CD8+ T cells. The DCs were generated by culturing monocytes in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. The DCs exposed to HIV-1 particles were co-cultured with healthy donor-derived blood T cells at a ratio of 1:20. Analyses by percent cell mortality, staining with propidium iodide and reactivity with Annexin V revealed the induction of apoptosis in both CD4+ and CD8+ target T cells. Further, this apoptosis occurred without stimulation with mitogens when the cell cycle of target T cells shifted from G0 to G1, probably due to the mitogenic effect of the DCs. Thus, induction of apoptosis in both CD4+ and CD8+ T cells occurred via interaction with DCs adsorbed with HIV-1 particles.
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PMID:Exposure of normal monocyte-derived dendritic cells to human immunodeficiency virus type-1 particles leads to the induction of apoptosis in co-cultured CD4+ as well as CD8+ T cells. 1080 98

Preliminary preclinical and clinical data suggest that granulocyte-macrophage colony-stimulating factor (GM-CSF) may decrease viral replication. Therefore, 105 individuals with AIDS who were receiving nucleoside analogue therapy were enrolled in a placebo-controlled, double-blind study and were randomized to receive either 125 microgram/m(2) of yeast-derived, GM-CSF (sargramostim) or placebo subcutaneously twice weekly for 6 months. Subjects were evaluated for toxicity and disease progression. A significant decrease in mean virus load (VL) was observed for the GM-CSF treatment group at 6 months (-0.07 log(10) vs. -0.60 log(10); P=.02). More subjects achieved human immunodeficiency virus (HIV)-RNA levels <500 copies/mL at >/=2 evaluations (2% on placebo vs. 11% on GM-CSF; P=.04). Genotypic analysis of 46 subjects demonstrated a lower frequency of zidovudine-resistant mutations among those receiving GM-CSF (80% vs. 50%; P=.04). No difference was observed in the incidence of opportunistic infections (OIs) through 6 months or survival, despite a higher risk for OI among GM-CSF recipients. GM-CSF reduced VL and limited the evolution of zidovudine-resistant genotypes, potentially providing adjunctive therapy in HIV disease.
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PMID:A randomized, placebo-controlled trial of granulocyte-macrophage colony-stimulating factor and nucleoside analogue therapy in AIDS. 1102 77


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