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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)

Knowing how mycobacteria exploit host cytokines to survive and which cytokines have important roles in host defense against mycobacteria should allow the use of these molecules in the treatment of mycobacterial infections. Both interleukin 2 and interferon gamma have been used to treat patients with leprosy, and granulocyte-macrophage colony-stimulating factor is presently being administered to AIDS patients infected with Mycobacterium avium.
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PMID:Recombinant cytokines for controlling mycobacterial infections. 771 35

Cryptococcus neoformans is a pathogenic yeast and a major cause of opportunistic infection in AIDS patients. It is commonly found in an acapsular form in the environment, and infection is likely to occur by inhalation. The lung provides a suitable environment for capsule synthesis, and once encapsulated, C. neoformans becomes resistant to phagocytosis. A stable acapsular mutant of the organism is readily ingested by murine macrophages in vitro, indicating entry via constitutively competent receptors. We demonstrate in this report that this process is inhibitable by particles derived from Saccharomyces cerevisiae that are rich in mannan and beta-glucan, as well as more purified forms of these glycans. Furthermore, ingestion of the acapsular form of C. neoformans induces a range of proinflammatory cytokines, including tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor, which, as we have previously shown, enhance ingestion of serum-opsonized encapsulated C. neoformans in vitro. We demonstrate that ingestion of the acapsular form of the organism also enhances ingestion of the pathogenic encapsulated form. This is dependent on the production of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor by the macrophages, since addition of neutralizing antibodies to both cytokines inhibited the observed increase in ingestion. Together, these data demonstrate that ingestion of acapsular C. neoformans is mediated via mannose and beta-glucan receptors on the macrophage surface and that this process activates macrophages for enhanced phagocytosis of the encapsulated form via production of macrophage-derived cytokines.
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PMID:Ingestion of acapsular Cryptococcus neoformans occurs via mannose and beta-glucan receptors, resulting in cytokine production and increased phagocytosis of the encapsulated form. 779 75

Current evidence suggests that the gut is the chief portal of entry for organisms of the Mycobacterium avium complex (MAC) in AIDS patients. Bacterial invasion of intestinal mucosa presumably occurs through epithelial cells, and M cells in the Peyer's patches, where the bacteria have contact with immunocompetent cells such as macrophages and T and B lymphocytes. As mucosal macrophages are probably the first line of defense against MAC, we examined their ability to inhibit intracellular growth of MAC when properly stimulated. Mouse intestinal macrophages were purified, infected with MAC 101, serovar 1, and MAC 86-2686, serovar 16, and subsequently stimulated with recombinant tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage colony-stimulating factor (M-CSF). Viable intracellular bacteria were quantitated at 24 h after infection and again after 4 days of infection. Stimulation with TNF-alpha, IFN-gamma, and GM-CSF, but not M-CSF, was associated with mycobacteriostatic and/or mycobactericidal activity in macrophages. Treatment with 10(3) U of TNF-alpha, GM-CSF, and IFN-gamma per ml at 24 h prior to infection with MAC resulted in a significant enhancement in killing of MAC at 4 days after infection, compared with that observed for macrophages exposed to cytokines after infection. When stimulated with lipopolysaccharide or live MAC, intestinal macrophages had produced significantly less TNF-alpha and transforming growth factor beta than had splenic and peritoneal macrophages, although the levels of production of interleukin 6 and interleukin 10 among the three populations of cells were similar. Intestinal macrophages can be stimulated with cytokines to inhibit the intracellular growth of MAC, but they have differentiated abilities to produce cytokines which can modulate the anti-MAC immune response.
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PMID:Response to stimulation with recombinant cytokines and synthesis of cytokines by murine intestinal macrophages infected with the Mycobacterium avium complex. 782 18

Variations in cytokine production in patients with human immunodeficiency virus (HIV) infection could be involved in the physiopathology and in the progression of the disease. Therefore we studied the level of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF alpha) produced in patients with HIV infection at stage II (asymptomatic seropositives) and stage IV (AIDS) of the CDC classification, by using an enzyme amplified sensitivity immunoassay. We measured the level of GM-CSF and TNF alpha in supernatant of phytohemagglutinin-activated peripheral blood mononuclear cells from patients and healthy individuals. In one out of 10 stage II patients and 4 out of 14 stage IV patients, we obtained higher levels of GM-CSF than the mean + 2 S.D. of controls, but in 3 stage IV patients with very low CD4+ T lymphocyte counts (< 50/mm-3) compared to other patients, the GM-CSF values were very low. High levels of TNF alpha were detected in 3 out of 10 stage II and 6 out of 11 stage IV patients. The high values of TNF alpha were associated with high values of GM-CSF in stage II and in most of AIDS patients except those with very low CD4+ T cell counts, who produced low levels of GM-CSF. Plasma levels of cytokines were evaluated in 10 stage II, 22 stage IV patients and 20 controls. Increased levels of GM-CSF (more than 9 pg/ml) were observed in the plasma from 8 out of 10 stage II patients and 17 out of 22 stage IV patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha in patients with human immunodeficiency virus (HIV) type 1 infection. 790 21

This prospective open trial evaluated the efficacy and tolerability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients with established neutropenia, considering as the main endpoint the clinical benefit to the patients regarding clearing of infection or resuming chemotherapy as initially planed. Adult patients (n = 28) with absolute neutrophil counts (ANC) < 10(9)/1 for 21 days were given a fixed dose (400 micrograms) of rhGM-CSF subcutaneously, for a total of 35 cycles. Causes of neutropenia were chemotherapy for acute leukaemia, lymphoma, myeloma and solid tumours, complications after bone marrow transplantation (BMT), and neutropenia associated with AIDS. Response (ANC to > 10(9)/l) occurred in 83% of rhGM-CSF cycles (29/35). Median time to response was 2.4 days (mean 6.7 days). Kinetics of response was dependent on diagnosis and treatment history. Fever abated with increasing ANC in 13/17 patients (76%) who entered the trial with hyperpyrexia. Treatment with rhGM-CSF allowed chemotherapy to be resumed on schedule in 7/9 relevant cycles. Toxicity was mild, leading to treatment interruption in only two cycles. In conclusion, rhGM-CSF was well tolerated and associated with a rise in ANC which appeared to result in immediate clinical benefit, including resolution of infection and resumption of scheduled chemotherapy.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in acquired or chemotherapy-induced neutropenia. An open clinical trial. 794 41

In this study, we examined the impact of the predominantly Th2-type lymphokines interleukin 13 (IL-13) and interleukin 4 (IL-4) on acute infection of human bronchoalveolar macrophages with a macrophage-tropic isolate of human immunodeficiency virus type 1 (HIV-1). Addition of 0.01-10 ng of IL-4 or IL-13 per milliliters significantly blocked HIV-1 replication in infected cells, judging from levels of reverse transcriptase and p24 antigen in the supernatants of infected cells. Both IL-4 and IL-13 were almost as efficient as interferon-gamma (IFN-gamma) in preventing HIV-1 replication, when given in equivalent amounts. Moreover, neither IL-13 nor IL-4 interfered with the IFN-gamma-mediated enhancement of anti-HIV-1 activity in alveolar macrophages. Both IL-4 and IL-13 interfered with enhanced replication of HIV-1 in macrophages pulsed with the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). Interleukin 13 also prevented HIV-1 release from peripheral blood mononuclear cells in a cocultivation experiment with feeder cells from a seronegative subject. These data suggest that Th2-derived lymphokines have significant anti-HIV-1 activity in cells of the macrophage lineage, although they may enhance the susceptibility of HIV-1-infected subjects to some opportunistic pathogens.
AIDS Res Hum Retroviruses 1994 Jul
PMID:Interleukin 13 and interleukin 4 protect bronchoalveolar macrophages from productive infection with human immunodeficiency virus type 1. 798 85

The number of cases HIV-associated non-Hodgkin's lymphoma continues to increase as the AIDS epidemic grows. Approximately 3% of AIDS-defining illnesses are non-Hodgkin's lymphoma. The number of non-Hodgkin's lymphoma cases may actually be higher because many cases go unreported. There is also evidence that increasing numbers of patients who are surviving longer on antiretroviral therapy are developing non-Hodgkin's lymphoma. A majority of HIV-related lymphomas are large cell, either high-grade immunoblastic or aggressive intermediate grade, diffuse cleaved, or small noncleaved (Burkitt's-like). HIV-related non-Hodgkin's lymphomas behave aggressively. They are predominantly extranodal and often show unusual patterns of organ involvement. They are typically stage III or IV at the time of diagnosis. Current treatment strategies involve the use of combination chemotherapy regimens with or without antiretroviral therapy. Current studies are evaluating the efficacy of low-dose chemotherapy regimens versus standard-dose regimens with granulocyte-macrophage colony-stimulating factor support. New strategies for treating AIDS-associated non-Hodgkin's lymphoma will incorporate our current knowledge of AIDS-related lymphoma pathogenesis. Factors that reflect a patient's state of immunodeficiency seem to be the most important prognostic features determining clinical outcome after treatment. Patients with good prognostic features may benefit the most from aggressive treatment regimens. AIDS-related primary central nervous system lymphomas continue to comprise approximately 15% of AIDS-related non-Hodgkin's lymphoma cases. Treatment is limited. Although whole-brain radiation therapy can result in an improved neurologic status, the median survival remains 3 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical aspects of HIV-related lymphoma. 821 98

Recombinant cytokines are now available for clinical use. Several colony-stimulating factors (CFS) have been identified which induce activation, proliferation and maturation of myeloid lineage cells. Recent therapeutic trials with granulocyte-macrophage colony-stimulating factors (GM-CSF) in association with chemotherapy, bone marrow transplantation and leukemia treatment are reviewed. GM-CSF as primary treatment for myelodysplasia and other types of bone marrow failure is also of interest. Colony-stimulating factor therapy in AIDS may be useful in order to reduce myelodepression caused by antiviral treatment and chemotherapy for associated malignancies like Kaposi's sarcoma. However, the effect of neutrophil count increase on infection is far from clear, and the real benefit of GM-CSF in cancer therapy has yet to be demonstrated.
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PMID:Therapeutic use of granulocyte-macrophage colony-stimulating factor (GM-CSF). A review of recent experience. 836 27

Azidothymidine (AZT) has been demonstrated to increase platelet counts in patients suffering from acquired immunodeficiency syndrome (AIDS). However, the ability of long-term AZT treatment to sustain increases in platelet counts is controversial. We have recently demonstrated that AZT elevates the levels of circulating platelets in both normal C57BL/6 mice and mice made immunodeficient by infection with LP-BM5 murine leukemia virus (MAIDS mice). We therefore studied the effect of long-term AZT administration on platelet formation in both normal and MAIDS mice. Peripheral blood indices, levels of femoral and splenic megakaryocyte colony forming units (CFU-MK), and plasma levels of cytokines important in platelet formation-interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF)--were examined. Platelet counts remained elevated throughout a 120-day AZT treatment period. Splenic CFU-MK were not significantly changed in MAIDS mice, except at day 15 when they were elevated. Splenic CFU-MK were significantly decreased in normal mice at days 8 and 120, and increased at day 30. Bone marrow CFU-MK were increased by AZT treatment at all time points tested in both normal and MAIDS mice. Plasma levels of GM-CSF were unchanged by AZT treatment in both normal and MAIDS mice. Plasma levels of IL-6 were unchanged in AZT-treated normal mice but decreased in AZT-treated MAIDS mice. These results indicate that long-term AZT treatment maintains elevated levels of platelets in both normal and MAIDS mice and affects CFU-MK colony formation. Our studies add to a growing body of work suggesting that AZT can ameliorate thrombocytopenia associated with HIV disease.
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PMID:Sustained elevation of platelet counts by long-term azidothymidine treatment of immunosuppressed mice. 845 34

Granulocytopenia is a complication of human immunodeficiency virus disease, as well as a toxic manifestation of zidovudine therapy. To evaluate pharmacokinetic and pharmacodynamic relationships, 11 AIDS-AIDS-related complex patients who had developed zidovudine-associated granulocytopenia (mean absolute neutrophil count, 1,077/mm3) were examined after addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to zidovudine. GM-CSF was administered as a daily (1.0 or 0.3 micrograms/kg) or every-other-day (0.3 micrograms/kg) subcutaneous dose over a 28-day period. Zidovudine was continued at the same daily dosage as was previously being administered. Of 11 patients, 7 (1.0 micrograms/kg, n = 5; 0.3 micrograms/kg, n = 2) had a pharmacologic response to GM-CSF with an increase to a mean absolute neutrophil count of 3,189 cells per mm3 at 4 weeks (P < 0.05). The peak concentration of GM-CSF in plasma ranged from 11.5 to 84.4 pg/ml, and the time to peak ranged from 1 to 3 h. No correlation between GM-CSF disposition and hematologic response was noted. A decreased plasma zidovudine-glucuronide/zidovudine ratio was noted after 1 week of GM-CSF, and an increase in the area under the plasma concentration-versus-time curve for zidovudine was found in three patients after 4 weeks. Low doses of GM-CSF can raise the granulocyte count in patients with zidovudine-induced neutropenia. The use of GM-CSF and zidovudine may represent a viable treatment option for persons with human immunodeficiency virus infection who develop neutropenia while receiving zidovudine but do not tolerate alternative nucleoside analogs. Further studies are needed to assess the complex interaction between these two agents.
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PMID:Pharmacokinetics and pharmacodynamics of granulocyte-macrophage colony-stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex. 846 Sep 20


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