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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)

The recombinant cytokines are increasingly important therapeutic agents for patients with AIDS. Recombinant interferon-alpha has demonstrated antitumor and antiretroviral activities in patients with Kaposi's sarcoma. Limited studies with interferon-beta suggest that it also has antitumor effects in patients with Kaposi's sarcoma, but interferon-gamma appears to be ineffective in controlling this tumor. The hematopoietic growth factors, including erythropoietin, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been evaluated in several populations of human immunodeficiency virus (HIV)-infected individuals. The combination of G-CSF and recombinant human erythropoietin completely reversed the zidovudine-induced neutropenia of AIDS patients but was only partially effective in reversing anemia. In several clinical trials, GM-CSF induced marked increases in leukocyte counts and improved neutrophil function in some AIDS patients. In severely immunocompromised patients with disease caused by HIV who were receiving therapy with either G-CSF or GM-CSF, opportunistic infections continued to occur despite increases in circulating white blood cell counts. Recombinant cytokines may be used in the future in AIDS patients as adjunctive treatment with myelosuppressive antibiotics and chemotherapeutic drugs, as a possible means of enhancing host defense, or as agents of immune reconstitution.
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PMID:Use of recombinant interferons and hematopoietic growth factors in patients infected with human immunodeficiency virus. 196 13

To evaluate the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) on patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) who were intolerant to zidovudine because of neutropenia, we performed a randomized, open-label study in which patients were assigned to one of two groups. Zidovudine was discontinued in group A patients before instituting GM-CSF treatment and was restarted in a graduated fashion over 4 weeks. Group B patients continued on full-dose (1,200 mg/d) zidovudine therapy while beginning GM-CSF therapy. A total of 17 patients were entered, eight in group A and nine in group B. Five of eight patients in group A and seven of nine in group B had a history of Pneumocystis carinii pneumonia (PCP). All were homosexual males, except one female in group A who was the sex partner of a bisexual male with AIDS. All patients had neutropenia (absolute neutrophil count [ANC] less than 1,000/microL) while taking full-dose zidovudine. The mean CD4 (+/- SD) lymphocyte level was 37 (+/- 29)/microL and 39 (+/- 44)/microL in groups A and B, respectively. After randomization, patients were begun on subcutaneous GM-CSF at a dose of 1.0 microgram/kg/d. Patients in group A received 2 weeks of daily GM-CSF, at which time zidovudine was restarted if the ANC was greater than 1,000/microL; if the ANC was less than 1,000/microL, the dose of GM-CSF was increased to 3.0 micrograms/kg, and at 2-week intervals either zidovudine was restarted or the dose of GM-CSF was increased to 5 micrograms/kg and then 10 micrograms/kg, to maintain the ANC greater than 1,000/microL. Group B patients received full-dose zidovudine concurrently with GM-CSF administration. The dose of GM-CSF was increased every 2 weeks if necessary to keep the ANC greater than 1,000/microL while maintaining full-dose zidovudine therapy. Patients in each group showed an increase in total white blood cell (WBC) count. Neutrophils and eosinophils were responsible for the majority of this increase. Patients in group A had a more rapid increase in WBC than those in group B; however, by week 8, the WBC in each group was essentially equal. Viral replication as measured by human immunodeficiency virus (HIV) p24 antigen (Ag) was decreased in four patients in each group, increased in one patient in each group, and remained unchanged in the remainder. The ability to culture virus from peripheral blood mononuclear cells was not changed by the regimen. The major toxicities of the regimen were fever and malaise.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor ameliorates zidovudine-induced neutropenia in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex. 174 82

The role of placental cells in transplacental transmission of human immunodeficiency virus type 1 (HIV 1) was investigated. Placental macrophages and trophoblasts, which together represent the main cell components of the placenta, were cultivated separately and then compared to foetal monocyte-derived macrophages for susceptibility to HIV 1 infection. Placental macrophages treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) were less easily infected with HIV 1 than were GM-CSF-treated foetal monocyte-derived macrophages. HIV 1 replication in cocultures consisting of infected placental macrophages together with a highly HIV 1-permissive cell line (CEM) was detected persistently for at least 6 weeks by reverse transcriptase assay, even though placental macrophages expressed no detectable CD4 receptor, as indicated by indirect immunofluorescence. HIV 1-specific DNA sequences were also detected in infected placental macrophages. Trophoblasts exhibited no detectable CD4 expression and did not support the replication of HIV 1, although low levels of HIV 1-specific DNA sequences could be detected in infected trophoblasts. Placental macrophages or trophoblasts (or both) may thus play an important role in transplacental HIV 1 transmission.
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PMID:Replication of human immunodeficiency virus type 1 in primary cultured placental cells. 189 50

A 4-year-old female with severe combined immunodeficiency (SCID) had normal numbers of T cells in circulation and normal T cell subsets. However, her T cells proliferated poorly to mitogens and did not proliferate to antigens or to anti-CD3 mAb. Interleukin-2 (IL-2) receptor expression was normal but IL-2 synthesis was undetectable. The addition of recombinant IL-2 to a mitogen-stimulated culture resulted in normalization of the proliferative response. Northern blot analysis of total RNA derived from the patient's T cells revealed a weak or absent expression of mRNA coding for IL-2, IL-3, IL-4, and IL-5. In contrast, there were normal amounts of mRNA coding for granulocyte-macrophage colony-stimulating factor (GM-CSF). Tumor necrosis factor and IL-6 production was also normal. Nuclear run on transcriptional assays revealed markedly decreased levels of newly initiated nuclear transcripts coding for IL-2, IL-3, IL-4, and IL-5 and normal levels of GM-CSF transcripts in patient relative to control lymphocytes. These results indicate that the patient's T cells suffered from a defect affecting the transcription of multiple T cell lymphokines and suggest that abnormalities affecting the production of T cell lymphokines may underlie some of the primary immunodeficiency diseases.
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PMID:Novel immune deficiencies: defective transcription of lymphokine genes. 193 9

The combined use of zidovudine (ZDV) and interferon (IFN) alfa-2a has been shown to have antiretroviral and antitumor potential benefit in the treatment of acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). However, the clinical use of this combination is frequently complicated by the overlapping myelotoxicity of these agents. We report here the results of a phase I/II study in which granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for those KS patients who became neutropenic while receiving ZDV (1,200 mg/d) and IFN (9 x 10(6) U/d). Nineteen of 29 patients (66%) developed an absolute neutrophil count (ANC) of less than 1,000 cells per cubic millimeter and were begun on GM-CSF. All experienced a prompt increase in the ANC. Those patients receiving GM-CSF/ZDV/IFN alfa-2a had an improved end of study ANC when compared with the ZDV/IFN alfa-2a group, but did not have an increased rate of tumor response, end of study CD4 cell count, or improvement in any other hematologic variable. The use of GM-CSF was not associated with increased toxicity and, in particular, was not associated with a change in serum human immunodeficiency virus (HIV) p24 antigen. Tumor response was noted in 50% of the assessable patients (33% overall) despite "high-risk" characteristics in 80%. Of the responding patients, seven were on GM-CSF and might have otherwise required an alteration in ZDV/IFN alfa-2a dose level. Further study of GM-CSF as an alternate to dose modification of this (ZDV/IFN alfa-2a) and other combination therapies for AIDS patients is warranted.
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PMID:Granulocyte-macrophage colony-stimulating factor mitigates the neutropenia of combined interferon alfa and zidovudine treatment of acquired immune deficiency syndrome-associated Kaposi's sarcoma. 196 May 65

A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
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PMID:Antiretroviral therapy and immunomodulators in patients with AIDS. 201 46

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.
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PMID:Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial. 203 29

Because polymorphonuclear neutrophils are the most important component of host defense against bacteria, we assessed their function in 13 children with asymptomatic and 12 with symptomatic infection with human immunodeficiency virus type 1 (HIV-1), and compared their values with healthy adult control values. The functions assessed were (1) chemotaxis, (2) bacterial phagocytosis, (3) superoxide generation, and (4) bactericidal activity. Chemotaxis of polymorphonuclear neutrophils toward the chemoattractant N-formylmethionyl leucyl phenylalanine (FMLP) was significantly decreased in symptom-free infected children compared with control subjects (p less than 0.0001), but was increased in children with symptomatic infection (p less than 0.025). Bactericidal activity of the neutrophils against Staphylococcus aureus was defective in 8 of 12 children with asymptomatic infection (p = 0.016), and in 8 of 9 children with symptomatic infection (p less than 0.00001). Superoxide generation by polymorphonuclear neutrophils on stimulation with FMLP and phagocytosis of S. aureus were normal. Serum from patients with symptomatic HIV-1 infection was not as efficient in low concentrations as normal serum in the ability to opsonize S. aureus. The in vitro bactericidal defect was partially corrected by granulocyte-macrophage colony-stimulating factor (GM-CSF). The results suggest that both cellular (neutrophils) and humoral defects contribute to the increased incidence of bacterial infections in HIV-1-infected children, and that GM-CSF may improve the defective bactericidal activity of polymorphonuclear neutrophils in these patients.
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PMID:Impairment of neutrophil chemotactic and bactericidal function in children infected with human immunodeficiency virus type 1 and partial reversal after in vitro exposure to granulocyte-macrophage colony-stimulating factor. 217 Jun 9

The alveolar macrophage (AM), as a representative human tissue macrophage, was used in an in vitro system to examine the anti-human immunodeficiency virus type-1 (HIV-1) activity of zidovudine (AZT) and granulocyte-macrophage colony-stimulating factor (GM-CSF). AMs were infected with the IIIB strain of HIV-1 and exposed to AZT (1 mumol/L), GM-CSF (30 U/mL), a combination of AZT (1 mumol/L)/GM-CSF (30 U/mL), or medium control. At 10 or 20 days post-infection, phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear leukocytes (PBMLs) were added to the AM cultures as stimulated target cells. AZT effectively suppressed HIV replication and prevented transfer/amplification in target PBMLs as long as the drug was maintained in the medium. GM-CSF neither suppressed nor augmented HIV replication. The combination of AZT/GM-CSF was comparable with AZT alone in suppressing both the initial infection of AMs and the transfer to target PBMLs as long as the agents were maintained in the cultures. However, when the drugs were removed at the same time that PHA-stimulated PBMLs were added to the culture, the combination of AZT/GM-CSF was found to be more effective than AZT alone in preventing the transfer/amplification of HIV in the target lymphocytes. These results suggest that (1) AZT is effective in inhibiting HIV-1 infection in mononuclear phagocytes; (2) GM-CSF neither inhibits nor augments the replication of the IIIB strain of HIV in human AMs; and (3) the combination of AZT and GM-CSF may have an enhanced anti-HIV-1 activity compared with AZT alone. Clinical trials with the two agents in combination appear warranted.
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PMID:Effect of zidovudine and granulocyte-macrophage colony-stimulating factor on human immunodeficiency virus replication in alveolar macrophages. 217 2

Interest in human dendritic cells (DC) has been heightened recently by the discovery that this cell type is a primary target of the human immunodeficiency virus, the causative agent of AIDS. DC are bone marrow-derived cells with an extraordinarily potent ability to promote the immunological activity of T lymphocytes. Unfortunately, since DC constitute less than 0.5% of peripheral blood mononuclear cells and die within a few days of their isolation, they are not readily accessible to study. We report here that granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine with well-recognized effects on granulocyte and macrophage maturation, profoundly affects the morphology and viability of DC isolated from peripheral blood. GM-CSF not only promotes DC survival but also induces DC differentiation to mobile, reversibly adherent cells with long-branched projections. DC cultured in GM-CSF survive for up to 6 wk and retain their ability to stimulate the proliferation of T cells in allogeneic and autologous mixed leukocyte reactions.
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PMID:Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro. 217 70


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