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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of granulocyte/macrophage colony-stimulating factor (GM-CSF) by peripheral blood (PB) light density mononuclear cells (LD-MNC), CD2+ T lymphocytes and purified CD4+ T lymphocytes was investigated in 20 human immunodeficiency virus type 1 (HIV-1) seropositive (WRII-III) individuals in comparison with 18 normal controls. GM-CSF in supernatants of stimulated cultures was determined by biological and immunoenzymatic assays. GM-CSF production by LD-MNC, CD2+ T lymphocytes and purified CD4+ T lymphocytes was significantly (p less than 0.01) reduced in HIV-1 infected individuals, especially in patients at the more advanced stages of the disease. Moreover, the number of circulating granulocyte/macrophage colony-forming units (CFU-gm) was significantly (p less than 0.01) reduced in HIV-1 seropositive subjects (31.5 +/- 4.4) compared with normal controls (78 +/- 10). There was a positive correlation (r = 0.720, p less than 0.01) between CFU-gm and GM-CSF production by LD-MNC in HIV-1 seropositive individuals. On the other hand, the absolute number of CD4+ lymphocytes did not correlate with GM-CSF production by LD-MNC (r = 0.158) or CD2+ T lymphocytes (r = 0.225). These data indicate that the impaired production of GM-CSF in HIV-1-infected individuals is not only due to a reduction in CD4+ T lymphocytes, but also to a qualitative impairment of these cells which may contribute to the loss of circulating hematopoietic progenitors in HIV-1-infected subjects.
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PMID:Impaired GM-CSF production by cultured light density mononuclear cells and T lymphocytes correlates with the number of circulating CFU-gm in HIV-1 seropositive subjects. 167 6

HIV infection is associated with a long period of clinical latency before the development of symptoms and HIV-related disease. Two chronically HIV-infected cell lines, U1 (promonocytic) and ACH-2 (T-lymphocytic) have been developed as models for studying the mechanisms governing viral latency and the reactivation of virus expression. We have previously shown that a variety of physiologic stimuli, including cytokines and cell stress, can up-regulate HIV expression from these cell lines. In this study we demonstrate that heat shock can also up-regulate the production of virus from both ACH-2 and U1 cells. Heat induction of virus appears to be mediated at the transcriptional level as established in long terminal repeat-chloramphenicol acetyl transferase transient transfection experiments with the use of U937 cells. This inductive effect in part requires the NF-kappa B-binding region of the HIV-long terminal repeat. Furthermore, although physiologic levels of heat are not sufficient to directly induce virus production from these cells, these temperatures are able to synergistically enhance virus production in U1 cells stimulated with IL-6 and granulocyte macrophage-CSF. In contrast, the inductive effect of other cytokines (i.e., TNF-alpha) was not affected by heat stimulation. These in vitro observations suggest that the hyperthermia associated with opportunistic infections, particularly in conjunction with certain cytokines that are released during immune reactions, may play a role in the in vivo induction of HIV expression in infected cells.
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PMID:Heat shock induction of HIV production from chronically infected promonocytic and T cell lines. 169 94

Monocytes cultured 7 to 10 days in recombinant human macrophage CSF (MCSF) were greater than 400-fold more susceptible to HIV infection than an equal number of cells cultured in medium alone. Levels of reverse transcriptase activity and p24 Ag in culture fluids of monocytes treated with MCSF 1 wk before and continuously after HIV infection were significantly greater than those of control cells cultured without MCSF. HIV-induced cytopathic effects in the MCSF-treated cultures also increased in both frequency and extent. At any given viral inoculum, the frequency of HIV-infected cells, the level of HIV mRNA/infected cell, and the level of proviral DNA/infected culture in MCSF-treated monocyte cultures were dramatically greater than those in control cultures. These differences were directly related to MCSF concentration to a maximum between 750 and 1000 U/ml MCSF, and were evident at all time points examined through 5 wk. None of the preceding effects was observed when MCSF was added at the time of or 1 wk after HIV infection. These data suggest that the predominant effect of MCSF for control of HIV infection is on the monocyte itself, not the virus. If these in vitro observations extend to the HIV-infected patient, then the variable levels of MCSF in tissue or blood may determine both the susceptibility of macrophages to virus infection and the extent of virus replication in infected cells.
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PMID:Enhanced HIV replication in macrophage colony-stimulating factor-treated monocytes. 170 95

To define the relationship between human immunodeficiency virus type 1 (HIV-1) infection in hematopoietic stem cells and virus production by their progeny, we performed kinetic studies infecting bone marrow (BM) stem cells and culturing them in the presence of hematopoietic growth factors. CD34-positive (CD34+), CD4-negative (CD4-) BM cells were isolated and infected in vitro with the monocytotropic HIV-1JR-FL strain or the laboratory-maintained HTLV-IIIB strain at a high multiplicity of infection. The cells were susceptible to productive infection only with HIV-1JR-FL, and virus production as measured by p24 protein release was markedly increased (more than fivefold) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). Macrophage CSF (M-CSF) was less stimulatory and granulocyte CSF (G-CSF) had no effect on virus production. Virus production coincided with proliferation of mononuclear phagocytes but was not related to granulocytic proliferation in G-CSF-treated BM cultures. Although peak virus production from GM-CSF-treated macrophages occurred 2 to 3 weeks after infection, peak virus production in infected stem cells was observed 5 to 6 weeks after. Enhancement in virus production had a more rapid onset when CD34+/CD4- cells were cultured in the presence of both GM-CSF and IL-3 for 7 or 14 days. Under these conditions there was a 10-fold enhancement in virus production after 7 days of preincubation and a 50-fold enhancement after 14 days. These data indicate that while the stem cell compartment may be susceptible to infection with a monocytotropic HIV-1 strain, productive and sustained infection is realized only after macrophage differentiation. The lack of effect of G-CSF on virus production is likely because of the limited effect of this hematopoietin on mononuclear phagocyte generation and function.
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PMID:Macrophage-active colony-stimulating factors enhance human immunodeficiency virus type 1 infection in bone marrow stem cells. 201 93

Human immunodeficiency virus (HIV) infection is associated with multiple defects in immune regulation and hematopoiesis. These defects include decreased proliferation of hematopoietic progenitor cells and increased destruction of mature cells. There are also disturbances of regulatory cytokines. As a result, hematopoietic cytopenias are common and the tolerance of myelosuppressive therapy is poor. One successful approach to the management of these clinical problems is the use of hematopoietic growth factors. To date, three agents have been studied in patients with HIV infection. In a Phase I trial, granulocyte macrophage-colony stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, alpha-interferon, and antineoplastic therapy. In a placebo-controlled trial, erythropoietin (EPO) decreased transfusion requirements and corrected anemia in the majority of patients receiving zidovudine. In a Phase I/II trial, granulocyte colony-stimulating factor (G-CSF) also corrected leukopenia and neutrophil defects in patients with AIDS without altering HIV expression. Combined G-CSF and EPO treatment corrected both anemia and leukopenia and reduced zidovudine toxicity. New combinations of hematopoietic stimulants are being used to decrease the toxicity from cytotoxic chemotherapy in the treatment of AIDS-related malignancies. Future treatments with other recombinant cytokines may result in both reduction in myelosuppression from drug therapy and, possibly, reconstitution of the immune and hematopoietic systems of HIV-infected patients.
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PMID:The use of hematopoietic growth factors in HIV infection and AIDS-related malignancies. 171 6

Prophylactic treatment with human granulocyte colony stimulating factor (hG-CSF) affords significant protection against systemic infections caused by C. albicans in cyclophosphamide-treated but not in cortisone-treated mice. Localized candidosis in neutropenic mice does not respond to hG-CSF. Our data show that granulocytes play an important role in the immune defence against deep mycoses, but not against local infections. From our data it is reasonable to assume that prophylactic treatment with hG-CSF may augment the resistance of immunosuppressed patients to deep Candida infection, but it would be of little help against oral candidosis of HIV patients.
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PMID:Protective effect of human granulocyte colony stimulating factor (hG-CSF) on Candida infections in normal and immunosuppressed mice. 172 Nov 5

The remarkable ability of HIV to insinuate itself into the working of the immune system is the key of its success as an infectious agent. Given that the cytokine network regulates the immune responses, it is not surprising that cytokines can modulate HIV infection. GM-CSF, IL6 and TNF-alpha enhance HIV, but TGF-beta and HIF inhibits the virus. However, the anti-HIV activity of TGF-beta is restricted to myeloid cells, while HIF inhibits HIV in myeloid cells and in T-lymphocytes. HIF is produced by CEM cells after induction by an extract from pine cones. It is not an interferon and is likely a novel cytokine. It is pepsin-sensitive but trypsin-resistant and has an apparent molecular weight of 7-12 KDa. Apart from having anti-HIV activity, crude preparations of HIF also inhibit HTLV-1 virus but not HSV virus replication.
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PMID:Cytokine regulation of the human immunodeficiency virus (HIV). 172 85

We investigated monocyte-derived macrophage function in 25 HIV-positive patients, 19 in the CDC class III and 6 class IV; 17 were intravenous drug abusers (IVDA) and 8 were homosexual men. Macrophages from HIV-positive patients behaved normally in assays of superoxide anion (O2-) production and candidacidal activity. After 3 days' treatment with 200 U/ml recombinant interferon-gamma (rIFN-gamma) or 250 U/ml recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF), both control and HIV-positive patients' phagocytes expressed the activated state, as indicated by the increased O2- production in response to phagocytable or soluble stimuli; however, these cytokines did not enhance candidacidal activity. Compared to appropriate HIV-negative controls (18 healthy heterosexuals, 4 homosexuals and 4 IVDA), macrophages from 19 of the 25 HIV-positive patients presented a significant defect in their Fc receptor (FcR)-dependent phagocytosis, independently from the CDC stage, AZT therapy, or life style. Treatment of macrophages with rIFN-gamma impaired their capacity to ingest IgG-coated erythrocytes, both in controls and HIV-positive subjects. Treatment of phagocytes with rGM-CSF significantly increased their FcR-dependent phagocytosis in controls, whereas in HIV-positive patients and in HIV-negative homosexuals and IVDA only an upward tendency was observed. Although the mechanism of the impaired FcR-dependent phagocytosis in HIV-positive patients remain to be clarified, our results suggest that this functional defect may be secondary to phagocyte priming by circulating IFN-gamma in vivo. This macrophage alteration may be implicated in the immunodeficiency of HIV-positive patients. However, considering the potential role of FcRs in HIV infection enhancement, the defective FcR function might even be a protective mechanism against FcR-mediated HIV dissemination. In the light of these findings, the immunotherapeutic potential of IFN-gamma and GM-CSF in HIV infection merits further investigation.
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PMID:Monocyte-derived macrophage function in HIV-infected subjects: in vitro modulation by rIFN-gamma and rGM-CSF. 173 Jan 55

In this study we demonstrate that HIV-1-seropositive thrombocytopenic individuals, in contrast with immune thrombocytopenic purpura (ITP) patients, fail to have a compensatory increase of megakaryocytopoiesis. The in vitro growth of bone-marrow megakaryocyte progenitors (CFU-MK) and the production of granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1 and IL-6 by bone-marrow mononuclear adherent cells and peripheral blood (PB) light-density mononuclear cells were studied in 12 HIV-1-seropositive thrombocytopenic individuals with respect to 12 ITP patients and 15 normal controls. In HIV-1-seropositive thrombocytopenic individuals, CFU-MK size (number of megakaryocytes per colony) was similar to normal controls but significantly lower (P less than 0.05) than in ITP patients. IL-1 and IL-6 production was similar in the three groups of subjects. On the other hand, GM-CSF production by bone-marrow mononuclear adherent cells in HIV-1-seropositive thrombocytopenic individuals was similar to normal controls but significantly (P less than 0.05) lower than in ITP patients, whereas GM-CSF production by PB light-density mononuclear cells was markedly (P less than 0.05) defective compared with both normal controls and ITP patients. The positive correlation between number and size of CFU-MK and production of GM-CSF by bone-marrow mononuclear adherent cells, observed in all three groups of subjects, demonstrates the central role of GM-CSF in the control of megakaryocytopoiesis.
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PMID:Lack of compensatory megakaryocytopoiesis in HIV-1-seropositive thrombocytopenic individuals compared with immune thrombocytopenic purpura patients. 176 83

Ganciclovir is effective in halting or delaying the progression of cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). However, the development of neutropenia necessitates the interruption of ganciclovir therapy in 40-50% of AIDS patients. In an ongoing randomized, controlled trial, AIDS patients with CMV retinitis are receiving standard ganciclovir therapy or ganciclovir plus recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). rHuGM-CSF is administered by daily subcutaneous injections and is given in ascending doses based on the neutrophil response in the individual patient. Preliminary data obtained from 36 evaluable patients (21 receiving ganciclovir alone, 15 receiving ganciclovir plus rHuGM-CSF) suggest that rHuGM-CSF administration is associated with a trend toward a decrease in the proportion of patients developing an absolute neutrophil count (ANC) of less than 750 cells/microliter (40% vs. 59%), in the overall incidence of such neutropenic episodes (20 vs. 68), and in the duration of ganciclovir treatment interruption due to the development of an ANC of less than 500 cells/microliter (5.5 days vs. 10.1 days). rHuGM-CSF administration has been generally well tolerated, and no consistent proliferative effect of this agent on human immunodeficiency virus infection has been observed. Definitive conclusions regarding the coadministration of rHuGM-CSF and ganciclovir await completion of the trial.
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PMID:Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. 184 18


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