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)

To investigate the physiological role of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adaptation mechanisms of myelopoiesis to enhanced demand, we studied both cytokines and their myeloid target cells in hematologically healthy patients suffering from acute bacterial infections. Endogenous serum levels of G-CSF and GM-CSF, granulocyte-macrophage colony-forming cell (GM-CFC) concentrations, and differential counts were determined for the peripheral blood of 57 patients with clinically apparent bacterial infections (26 males and 31 females aged 16 to 89 years) and 18 healthy controls (8 males and 10 females aged 23 to 84 years). Patients were selected for acute-phase protein and at least two additional clinical signs reflecting a bacterial infection. Patients showed significantly higher numbers of myeloid progenitor cells than controls (median, 68 versus 26 GM-CFC/ml; P < or = 0.01). G-CSF but not GM-CSF levels were found to be elevated (> or = 50 to 863 pg/ml). In the acute stage of infection, progenitor and cytokine levels were not influenced by gender, differences in therapy, or localization of the infection. Progenitor and G-CSF levels were not associated with absolute neutrophil counts or C-reactive protein. However, a negative correlation between number of GM-CFC per milliliter and age (R = -0.47; P < or = 0.001) and an inverse relationship between the incidence of high GM-CFC concentrations and elevated G-CSF levels (phi = -0.34; P < or = 0.01) were found. Combining both parameters into a cytokine-progenitor pattern, we observed a highly significant age-dependent response of myelopoiesis to inflammation (P < or = 0.001). Younger patients had high progenitor counts (> 75 GM-CFC/ml) associated with G-CSF levels below 50 pg/ml, whereas for the older patients, the reverse pattern was predominant. The results indicate that the age-dependent myelopoietic response to acute bacterial infections is characterized by an inverse relationship between progenitor cells and G-CSF. The observed cytokine-progenitor patterns could have implications for therapy with G-CSF and the prognosis of infectious diseases.
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PMID:Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections. 752 29

Infection caused by organisms of the Mycobacterium avium complex is diagnosed in 50% to 60% of AIDS patients with the advanced stage of disease. Mycobacterium avium is an environmental bacterium that gains access to the host through both the gastrointestinal tract and the respiratory tract. After crossing the mucosal barrier Mycobacterium avium disseminates, infecting chiefly mononuclear phagocytes of the reticuloendothelial system. A number of cells of the immune system such as CD4+ T cells, natural killer cells and macrophages have been shown to be involved in the host response to Mycobacterium avium. The interaction between Mycobacterium avium and macrophages results in the production of immune-suppressive cytokines that inhibit the effector function of TH1 subtype CD4+ T cells, natural killer cells and macrophages, possibly allowing survival of Mycobacterium avium. Some cytokines such as tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor have been shown to induce mycobacteriostatic activity and mycobactericidal activity in infected macrophages. Over the next few years, much new information will certainly be gleaned about host-pathogen interactions, which will lead to a better understanding of the disease and possibly to the design of new forms of therapy.
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PMID:Immunobiology of Mycobacterium avium infection. 769 13

Drug induced agranulocytosis (DIA) is a potentially lethal disorder characterized by selective neutropenia. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been utilized for its treatment. We report four cases of DIA treated with GM-CSF at the dose of 5 micrograms/kg/day. The patients presented infectious diseases at diagnosis. Median days to obtain 1 x 10(9)/L neutrophils and a normal neutrophil count (NNC), were 7(5-9) and 7.5 (6-10) days, respectively. The infectious disease at diagnosis improved and all patients are alive at the moment of this report. No other adverse effects than thrombocytosis (two cases) and thrombocytopenia (one case) were observed. We consider that GM-CSF could be a safe and effective alternative in the treatment of DIA.
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PMID:Drug-induced agranulocytosis treated with granulocyte-macrophage colony stimulating factor. 807 66

Placental macrophages were isolated and cultured in vitro to investigate their susceptibility to HIV infection and possible role in vertical transmission of HIV. After 10 days of in vitro culture the cells were positive for nonspecific esterase and acid phosphatase and negative for myeloperoxidase and placental alkaline phosphatase. They expressed cell surface HLA-ABC, HLA-DR, CD45, as well as CD68 intracellularly, as detected by flow cytometry, confirming their macrophage lineage. Approximately 80% of cells expressed surface CD14. CD4 antigen was expressed at very low levels and was confirmed by antibody blocking experiments. Infection of placental macrophage cultures with HIV resulted in a transient peak of viral replication 3 to 7 days after infection, but no later rise in HIV was detected with culture of up to 60 days. HIV replication was not up-regulated by coculture with phytohemagglutinin-stimulated lymphocytes or by treating infected cultures with tumor necrosis factor alpha or granulocyte-macrophage colony-stimulating factor.
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PMID:HIV infection of placental macrophages: their potential role in vertical transmission. 808 96

Cytokines are key mediators of the immune system, dictating the quality of the host response to infection. The importance of such immune mediators to the development of immune and inflammatory responses has emerged from work in mouse and man, however it has now become necessary to produce the equivalent (and novel) cytokines in ruminants. Over the past three years recombinant DNA techniques have allowed the cloning of numerous ovine cytokines. These include interleukins -1, -2 and -3 (IL-1, -2 and -3), interferon-gamma (IFN-gamma), ovine trophoblast protein (oTP-1), tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The predicted amino-acid sequences of these ovine proteins show varying degrees of similarity with the equivalent human proteins thus explaining why some of the cytokines are not biologically cross-reactive between species. Recombinant ovine proteins have been produced for IFN-gamma, oTP-1, IL-1, IL-3 and GM-CSF. Their biological activities are very similar to those of their human counterparts. Although it is too early to tell whether the recombinant ovine proteins will be of use in the treatment or prophylaxis of infectious disease, work in cattle and pigs has indicated the potential usefulness of cytokines in this role.
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PMID:Current research on ovine cytokines. 822 Oct 42

Patients rendered T cell-deficient by advanced disease due to human immunodeficiency virus, an underlying neoplastic disorder, or immunosuppressive therapy are vulnerable to a select group of opportunistic infections. These infections, which often fail to respond to conventional therapy, provide the clinical setting in which the efficacy of treatment with cytokines can be tested. Particularly pertinent cytokines are those that activate macrophages and monocytes or enhance T-cell function. Experimental observations and emerging data from patients with intact T-cell function suggest that treatment with at least three cytokines, interferon-gamma, interleukin-2, and granulocyte-macrophage colony-stimulating factor (GM-CSF) may be of benefit. Each of these cytokines is already in clinical use, and each has therapeutic potential in a variety of different infectious disease. Patients with infections caused by opportunistic intracellular pathogens appear to be the most appropriate candidates for adjunctive cytokine therapy.
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PMID:Cytokines as antimicrobial therapy for the T cell-deficient patient: prospects for treatment of nonviral opportunistic infections. 827 6

There has been a growing body of evidence suggesting that CD4+ Th1/Th2 cell responses participate in pathologic and immunologic processes in infectious disease. Bacterial meningitis is a fatal disease of children and is associated with a spectrum of clinical syndromes. This study provides evidence of CD4+ enhanced interleukin (IL)-4 and IL-6 but decreased IL-2 and interferon-gamma (IFN-gamma) production, the induction of characteristic Th2 cell response cytokines in bacterial meningitis, which may play an important role in disease mechanism. Additionally, monocyte-induced enhanced IL-6, IL-8, and tumor necrosis factor-alpha production may be associated with distinct clinical features such as fever, seizures, and neurological sequelae. A striking finding was also the highly deficient monocyte-induced granulocyte-macrophage colony-stimulating factor production. Of particular interest, the CD(8+)-enhanced IFN-gamma production may be required for the cytolytic activity or protective response to be maintained in this disease. Taken together, these data reveal that monocytes and CD4+ (Th2) and CD8+ subsets produce distinct cytokines in bacterial meningitis, which may exert an immunoregulatory and immunopathologic effect and thus mediate some of the clinical manifestations of the disease.
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PMID:CD4+ Th2 cell response cytokine production in bacterial meningitis. 857 20

Infection of mice with Plasmodium berghei engendered a temporary appearance of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum. The peak of GM-CSF levels was detected at day 2 post-infection, and then gradually decreased. On the other hand, the number of committed stem cells for granulocytes and macrophages (CFU-GM) in bone marrow transiently decreased at day 2 post-infection, and then increased and peaked at day 6 post-infection. When the serum of P. berghei-infected mice was fractionated by gel chromatography on Sephacryl S-300, GM-CSF activity was detected as a single peak with an apparent molecular weight of 64 KDa. GM-CSF was entirely adsorbed to concanavalin A-Sepharose 4B affinity chromatography, and was sensitive to pronase digestion, indicating its glycoprotein nature. These results suggest that the circulating GM-CSF would contribute the increase of granulocyte-macrophage hemopoiesis in the early phase of malaria.
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PMID:Temporary appearance of a circulating granulocyte-macrophage colony-stimulating factor in lethal murine malaria. 918 64

Use of marijuana and cocaine is on the rise in the United States. Although pulmonary toxicity from these drugs has occasionally been reported, little is known about their effects on the lung microenvironment. We evaluated the function of alveolar macrophages (AMs) recovered from the lungs of nonsmokers and habitual smokers of either tobacco, marijuana, or crack cocaine. AMs recovered from marijuana smokers were deficient in their ability to phagocytose Staphylococcus aureus (p < 0.01). AMs from marijuana smokers and from cocaine users were also severely limited in their ability to kill both bacteria and tumor cells (p < 0.01). Studies using NG-monomethyl-L-arginine monoacetate, an inhibitor of nitric oxide synthase, suggest that AMs from nonsmokers and tobacco smokers were able to use nitric oxide as an antibacterial effector molecule, while AMs from smokers of marijuana and cocaine were not. Finally, AMs from marijuana smokers, but not from smokers of tobacco or cocaine, produced less than normal amounts of tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-6 when stimulated in culture with lipopolysaccharide. In contrast, the production of transforming growth factor-beta, an immunosuppressive cytokine, was similar in all groups. These findings indicate that habitual exposure of the lung to either marijuana or cocaine impairs the function and/or cytokine production of AMs. The ultimate outcome of these effects may be an enhanced susceptibility to infectious disease, cancer, and AIDS.
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PMID:Marijuana and cocaine impair alveolar macrophage function and cytokine production. 937 83

A recombinant vaccinia virus encoding the gene for granulocyte-macrophage colony-stimulating factor (rV-GM-CSF) was used to infect the poorly immunogenic murine colon adenocarcinoma cell line, MC-38. Infection of MC-38 tumor cells with rV-GM-CSF completely suppressed the growth of the MC-38 primary tumors, whereas progressively growing tumors were formed in mice injected with MC-38 cells infected with wild type V-Wyeth. Irradiation of the recipient B6 mice before implantation of rV-GM-CSF-infected tumor cells resulted in the development of progressively growing tumors. Moreover, in vivo T-cell depletion studies revealed that growth suppression of the rV-GM-CSF-infected tumor cells was dependent on the presence of both CD4+ and CD8+ T-cell subsets. Subsequent studies established that this immunity was long-lasting and antigen specific, as demonstrated by the protection of rV-GM-CSF-immunized mice from MC-38 tumor challenge but not from challenge with another syngeneic tumor cell type. No such effects were observed when MC-38 tumor cells were infected with recombinant vaccinia viruses expressing interleukin (IL)-2 or IL-6. The results demonstrate that paracrine release of biologically active murine GM-CSF by tumor cells infected with rV-GM-CSF enhances the intrinsic immunogenicity of a poorly immunogenic murine tumor. Presumably the augmentation of tumor immunogenicity induces an antigen-specific T-cell-dependent antitumor response that prevents the formation of primary tumors and protects mice from tumor challenge. Thus in this experimental model, GM-CSF functions as a highly effective vaccine adjuvant.
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PMID:Immunization with a syngeneic tumor infected with recombinant vaccinia virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) induces tumor regression and long-lasting systemic immunity. 940 50


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