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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 human cytokines granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin, and interleukin-2 (IL-2) have been manufactured and licensed. Studies have been carried out that investigate the use of G-CSF and GM-CSF to reverse leukopenia, as adjunctive therapy for HIV-associated infections and for novel approaches to treat HIV infection, including stem cell mobilization. In addition, studies that identified the role of erythropoietin in the management of anemia have been performed. Furthermore, the abilities of G-CSF and erythropoietin to permit the continued use of marrow suppressive agents that are key in managing HIV infection have been assessed. The aim of this review is to summarize these studies and to describe the reports that evaluate the use of IL-2 to enhance elevation of CD4 cell counts mediated by highly active antiretroviral therapy. This summary is important to the treating clinician in that it identifies the optimal use of these cytokines in current clinical practice as well as their potential future roles.
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PMID:Use of cytokines in human immunodeficiency virus-infected patients: colony-stimulating factors, erythropoietin, and interleukin-2. 1122 45

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.
Pediatr AIDS HIV Infect 1995 Oct
PMID:Growth hormone in HIV/AIDS: current uses and future prospects. 1136 93

A trial has been started to study granulocyte-macrophage colony-stimulating factor (GM-CSF) in people with AIDS. This drug may help people to produce additional infection-fighting white blood cells. Participants need to be on approved HIV drugs. The test will involve shots injected under the skin three times a week; half the participants will receive GM-CSF and the other half, placebo.
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PMID:Advanced AIDS treatment. 1136 87

A number of significant papers from the Eleventh Annual Houston Conference on AIDS in America are summarized. Topics include the current concepts in pathogenesis of HIV infection, the use of anti-HIV therapies, and drug interactions in HIV treatment. A session on HIV disease in children focused on the epidemiology and prevention of vertical transmission with Zidovudine, when to initiate therapy, and options for children who have failed current therapies. Studies using immune-based therapy have shown promise in treating HIV disease. New data from a study with sargramostim, an investigational agent for opportunistic infection prophylaxis, shows that the drug reduces viral loads and delays time to treatment failure. Pentafuside (T-20), the first of a new class of HIV drugs, fusion inhibitors, has been found to be safe and effective against HIV, although drug resistance may be associated with its use. Other sessions summarized progress in clearing HIV from viral reservoirs, the ethics of HIV research support from the drug industry and drug marketing, and a review of immune reconstitution studies among people on antiretroviral therapy. Sam Avrett of the AIDS Vaccine Advocacy Coalition (AVAC) summarized in his session the characteristics of a successful HIV vaccine and the need to have more people involved in vaccine advocacy as a means to ending the epidemic. Contact information is provided.
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PMID:Summaries from the Eleventh Annual Houston Conference on AIDS in America. 1136 19

Restoring and preserving immune function is a key component to successfully managing HIV-1 disease. Phase II/III studies have evaluated the safety and immunologic effects of immune-based therapies, including granulocyte-macrophage colony-stimulating factor, interleukin-2, and an inactivated HIV-1 immunogen, as adjuncts to antiretroviral therapy. Addition of each of these immune-based therapies to a background antiretroviral regimen enhanced, to varying degrees, immunologic function and suppression of viral replication in HIV-1-infected patients, suggesting a potential role for immune-based therapies in the treatment of HIV-1 disease. Further studies are needed to better characterize specific immunologic and virologic effects in different patient populations and to determine their impact on clinical outcomes.
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PMID:Improving immune function and controlling viral replication in HIV-1-infected patients with immune-based therapies. 1139 78

HIV can cross the intact epithelium of genital mucosae via Langerhans cells. Fresh Langerhans cells are known to express CD4 and CCR5. The presence of CXCR4 on the surface of cultured but not freshly isolated Langerhans cells has been described. In the present study, we demonstrate that CXCR4 was expressed by fresh Langerhans cells isolated and purified from epidermis. However, the percentage of Langerhans cells expressing CXCR4 or CCR5 increased during maturation of the cells in culture, especially in the presence of exogenous granulocyte-macrophage colony-stimulating factor. To determine whether CXCR4 was functional, freshly isolated Langerhans cells were infected with HIV LAI, a T-cell-tropic strain, and p24 protein production was measured in culture supernatants. p24 production was observed when infected Langerhans cells were cocultured with SupT1 cells. However, the presence of HIV provirus DNA was evidenced within the infected Langerhans cells by nested PCR. Ultrastructural studies confirmed the formation of syncytia when Langerhans cells were cocultured with SupT1 cells. Preincubation of Langerhans cells with azidothymidine or SDF-1-alpha, a natural ligand for CXCR4, prevented infection. These data demonstrated that CXCR4 is present on the surface of Langerhans cells freshly isolated from human skin epidermis and that this expression is functional.
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PMID:Functional HIV CXCR4 coreceptor on human epithelial Langerhans cells and infection by HIV strain X4. 1149 25

The topical application of DNA vaccine to the skin is a useful method of immunization because of its simplicity, painlessness and economy. But the immune responses that it elicits are relatively low. In this study, we administered human immunodeficiency virus type-1 (HIV-1) DNA vaccine with cytokine-expressing plasmids to the skin of mice by a new topical application technique involving prior elimination of keratinocytes using fast-acting adhesive. Our results revealed that the topical application of HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. Co-administration of the DNA vaccine with cytokine expression plasmids of IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by this new method raised the levels of both the HIV-specific cytotoxic T lymphocyte (CTL) response and delayed-type hypersensitivity (DTH) and facilitated the induction of substantial immune responses by DNA vaccine. Skin biopsy sections, thus, immunized showed significant increases of S-100 protein-positive dendritic cells (DCs). These results suggest that the topical application method described here is an efficient route of DNA vaccine administration and that the immune response may be induced by DNA plasmids taken in by DCs, Langerhans cells (LCs), or others such as antigen-presenting cells. This new topical application is likely to be of benefit in clinical use.
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PMID:Topical application of HIV DNA vaccine with cytokine-expression plasmids induces strong antigen-specific immune responses. 1156 44

The chemokine stromal cell-derived factor (SDF)-1 and its receptor, CXCR4, play important roles in human immunodeficiency virus type 1 (HIV-1) pathophysiology, leukocyte trafficking, inflammation, hematopoiesis, embryogenesis, angiogenesis, and cancer metastasis. The effects of cytokines on the regulation of CXCR4 function were investigated in human primary monocytes-macrophages. The expression of functional CXCR4 on the cell surface was demonstrated by the detection of ligand-induced Ca(2+) mobilization, chemotaxis, and ligand-induced receptor endocytosis. Surface CXCR4 expression was down-regulated by cytokines interleukin-4 (IL-4), IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and up-regulated by IL-10 and transforming growth factor-beta 1. Down-regulation was mediated post-translationally, in the absence of protein degradation, through an endocytotic mechanism. In contrast to SDF-1 alpha-induced CXCR4 endocytosis, cytokine-induced endocytosis of this receptor was independent of actin filament polymerization. GM-CSF increased the expression of G protein-coupled receptor kinase 3 (GRK3), beta-arrestin-1, Pyk2, and focal adhesion kinase (FAK). Cytokine treatment also increased the total and tyrosine-specific phosphorylation of CXCR4 as well as the phosphorylation of FAK on tyrosine 397. It also induced the formation of GRK3.CXCR4 or FAK.CXCR4 complexes. Infection of macrophages by primary R5X4 and X4 isolates of HIV-1 was inhibited by IL-4, IL-13, and GM-CSF, an effect that was associated with down-regulation of surface CXCR4 expression. These data indicate that ligand-dependent and ligand-independent endocytoses of CXCR4 are mediated by different mechanisms. Cytokine-induced endocytosis of chemokine receptors may be of therapeutic value in HIV-1 infection, inflammation, tumor metastasis, and defective hematopoiesis.
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PMID:Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages. 1166 82

Dendritic cells (DC), the most potent antigen-presenting cells (APC), have been implicated as the initial targets of HIV infection in skin and mucosal surfaces. DC can be generated in vitro from blood-isolated CD14(+) monocytes or CD34(+) hematopoietic progenitor cells in the presence of various cytokines. In this study, we investigated whether monocytes obtained from placental cord blood are capable of differentiation into dendritic cells when cultured with a combination of cytokines - granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). We then examined HIV infection, HIV receptor (CD4, CCR5) expression, and beta-chemokine [macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha, MIP-1beta)] production by placental cord monocyte-derived dendritic cells (MDDC) as compared to that of autologous cord monocyte-derived macrophages (MDM). Monocytes isolated from placental cord blood differentiate into DC after 7 days in culture with the mixture of cytokines, as demonstrated by development of characteristic DC morphology, loss of CD14 expression, and gain of CD83, a marker for mature DC. Mature cord MDDC had significantly lower susceptibility to M-tropic ADA (CCR5-dependent) envelope-pseudotyped HIV infection in comparison to autologous placental cord MDM, whereas there was no significant difference in virus replication in cord MDDC and MDM infected with murine leukemia virus envelope-pseudotyped HIV (HIV receptor-independent). This limited susceptibility of cord MDDC to M-tropic HIV infection may be due to lower expression of CD4 and CCR5 on the cell membrane and higher production of MIP-1alpha and MIP-1beta. These data provide important information toward our understanding of the biological properties of cord MDDC in relation to HIV infection.
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PMID:HIV-1 infection of placental cord blood monocyte-derived dendritic cells. 1167 7

We developed a method for applying HIV-1 DNA vaccine topically in mice. Topical application of DNA vaccine to the skin is useful against infections. To find a less expensive and less cumbersome vaccination method, we administered HIV-1 DNA vaccine to the skin of mice after elimination of keratinocytes using a fast-acting adhesive. HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. A high level of HIV-1-specific cytotoxic T lymphocyte response was also observed, and a high level of IFN-gamma and IL-4 production was induced by the improved skin application of DNA vaccine. High levels of both HIV-specific cytotoxic T lymphocyte and delayed type hypersensitivity in topical application were induced by coadministration of the DNA vaccine with IL-12 expression plasmids and granulocyte-macrophage colony-stimulating factor expression plasmids. These immune responses were inhibited by intradermal injection of anti-CD11c or anti-I-A/I-E antibody. Therefore, topical administration of DNA vaccine is an effective route, and may be very useful for the prevention of infectious diseases.
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PMID:Immunologic characterization of HIV-specific DNA vaccine. 1176 91


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