Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Granulocyte-macrophage colony-stimulating factor (GMCSF) is a hematopoietic protein that has been studied both in vitro and in vivo in human immunodeficiency virus (HIV) infection. Since both HIV infection primarily and zidovudine (formerly AZT) treatment secondarily may result in neutropenia, administration of GMCSF to persons with HIV infection is generating considerable interest. Despite in vitro studies demonstrating that the agent may stimulate HIV replication, in the presence of zidovudine a synergistic inhibition of replication occurs. Early clinical studies in patients with the acquired immunodeficiency syndrome indicate that GMCSF can raise neutrophil counts with or without concurrent zidovudine treatment. The long-term safety and tolerance of the combination has to be established.
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PMID:Granulocyte-macrophage colony-stimulating factor and zidovudine in the treatment of neutropenia and human immunodeficiency virus infection. 149 10

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

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

We studied the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the suppression of hematopoiesis associated with the use of the antiviral drug zidovudine (AZT) administered in vivo to normal mice, as determined by measuring peripheral blood indices, and assays of hematopoietic progenitors, i.e. erythroid (CFU-E/BFU-E), myeloid (CFU-GM), and megakaryocyte (CFU-Meg) from bone marrow and spleen. Previous studies from this laboratory have established that dose-escalation zidovudine induced a dose-dependent decrease in hematocrit, WBC, and platelets with altered populations of bone marrow and splenic erythroid, myeloid and megakaryocyte progenitors when administered to normal mice. Daily administration of GM-CSF (10 micrograms/kg/bw) was associated with altered peripheral blood indices and progenitor cells. Dose-escalation AZT, i.e. 0.1, 1.0 and 2.5 mg/ml, was associated with a comparable reduction in all indices, i.e. hematocrit, WBC, and platelets during the 6-week examination period. GM-CSF reduced zidovudine-induced myeloid toxicity (concentration < 2.5 mg/ml) which was associated with an increase in bone marrow and splenic CFU-GM. High concentration, i.e. 2.5 mg/ml still produced myelosuppression irreversible with GM-CSF. GM-CSF induced a reduction in circulating platelets following zidovudine treatment at weeks 2 and 4 with the 1.0 mg/ml and 2.5 mg/ml treatment groups respectively, compared to a persistent decrease in platelets in the presence of zidovudine alone. GM-CSF BFU-E were elevated indicating the restriction in erythoid differentiation was still present. These studies demonstrate GM-CSF influences myeloid and megakaryocyte recovery, but not the erythoid suppression associated with the antiviral drug zidovudine.
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PMID:Prevention of hematopoietic myeloid and megakaryocyte toxicity associated with zidovudine in vivo in mice with recombinant GM-CSF. 795 Sep 2

Splenopentin (DA SP-5) is a pentapeptide corresponding to the amino acid sequence 32-36 (Arg-Lys-Glu-Val-Tyr) of the splenic hormone splenin. We examined the influence of DA SP-5 on bone marrow progenitor cell (BMC) proliferation. DA SP-5 acts as a co-stimulant for recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in the induction of human BMC derived colony formation in vitro (colony-forming units). When exposed to DA SP-5 and thereafter to AZT and rHuGM-CSF, BMCs show a colony-forming response similar to that after cultivation with the rHuGM-CSF alone. In contrast, when exposed to AZT and rHuGM-CSF (and not preincubated with DA SP-5) the colony formation was reduced. A similar pentapeptide thymopentin (Arg-Lys-Asp-Val-Tyr) did not influence colony formation by human BMCs. We assume that DA SP-5 could support therapeutic effects of rHuGM-CSF.
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PMID:The effect of splenopentin (DA SP-5) on in vitro myelopoiesis and on AZT-induced bone marrow toxicity. 850 37

Dendritic cells (DC) were sorted on day 8 from cultures of CD34(+) cells with stem cell factor/Flt-3 ligand/ granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor-alpha (TNF-alpha)/interleukin-4 (IL-4). Exposing immature CCR5(+)CXCR4(lo/-) DC to CCR5-dependent human immunodeficiency virus (HIV)-1Ba-L led to productive and cytopathic infection, whereas only low virus production occurred in CXCR4-dependent HIV-1LAI-exposed DC. PCR analysis of the DC 48 hours postinfection showed efficient entry of HIV-1Ba-L but not of HIV-1LAI. CD40 ligand- or monocyte-conditioned medium-induced maturation of HIV-1Ba-L-infected DC reduced virus production by about 1 Log, while cells became CCR5(-). However, HIV-1Ba-L-exposed mature DC harbored 15-fold more viral DNA than their immature counterparts, ruling out inhibition of virus entry. Simultaneously, CXCR4 upregulation by mature DC coincided with highly efficient entry of HIV-1LAI which, nonetheless, replicated at the same low level in mature as in immature DC. In line with these findings, coculture of HIV-1Ba-L-infected immature DC with CD3 monoclonal antibody-activated autologous CD4(+) T lymphocytes in the presence of AZT decreased virus production by the DC. Finally, whether they originated from CD1a+CD14(-) or CD1a-CD14(+) precursors, DC did not differ as regards permissivity to HIV, although CD1a+CD14(-) precursor-derived immature DC could produce higher HIV-1Ba-L amounts than their CD1a-CD14(+) counterparts. Thus, both DC permissivity to, and capacity to support replication of, HIV is primarily determined by their maturation stage.
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PMID:The susceptibility to X4 and R5 human immunodeficiency virus-1 strains of dendritic cells derived in vitro from CD34(+) hematopoietic progenitor cells is primarily determined by their maturation stage. 1033 95

Recombinant human growth hormone (rhGH) and its primary induced product, insulin-like growth factor-I (IGF-I), have beneficial effects on a myriad of syndromes associated with catabolic metabolism in children and in adults. Their ability to promote nitrogen retention and protein synthesis and to enhance lipolysis has translated into significant increases in body weight, lean body mass, and sense of well-being among HIV+ individuals with wasting syndromes. These changes, first observed in limited phase I studies, have now been confirmed by two large, controlled clinical trials. The alterations are consistent with the low GH and/or IGF-I levels observed in HIV infection, as well as the relative resistance to GH. Whether long-term outcome in HIV disease is altered by such therapies remains to be determined, however. The ability of GH to augment cellular immune function and modulate T lymphocyte trafficking in animal models of immune suppression has also led to examination of its impact on CD4+ T cell counts and viral load in HIV infection. There is currently little evidence that short-term rhGH administration has any lasting impact on T cell biology in the setting of HIV disease. However, preliminary reports that, in vitro, GH alters immune cell apoptosis and enhances the efficacy of Zidovidine (AZT), similar to changes observed with granulocyte-macrophage colony-stimulating factor, may lead to additional uses for GH. Studies to define the mechanism of action of GH and IGF-I on normal and abnormal immune homeostasis in children and adults should enhance our ability to design effective treatments for those with acquired immune deficiency syndrome (AIDS) and perhaps other wasting and immune suppressive disorders.
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PMID:Growth hormone in HIV/AIDS: current uses and future prospects. 1136 93