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 evaluate the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) on patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) who were intolerant to zidovudine because of neutropenia, we performed a randomized, open-label study in which patients were assigned to one of two groups. Zidovudine was discontinued in group A patients before instituting GM-CSF treatment and was restarted in a graduated fashion over 4 weeks. Group B patients continued on full-dose (1,200 mg/d) zidovudine therapy while beginning GM-CSF therapy. A total of 17 patients were entered, eight in group A and nine in group B. Five of eight patients in group A and seven of nine in group B had a history of Pneumocystis carinii pneumonia (PCP). All were homosexual males, except one female in group A who was the sex partner of a bisexual male with AIDS. All patients had neutropenia (absolute neutrophil count [ANC] less than 1,000/microL) while taking full-dose zidovudine. The mean CD4 (+/- SD) lymphocyte level was 37 (+/- 29)/microL and 39 (+/- 44)/microL in groups A and B, respectively. After randomization, patients were begun on subcutaneous GM-CSF at a dose of 1.0 microgram/kg/d. Patients in group A received 2 weeks of daily GM-CSF, at which time zidovudine was restarted if the ANC was greater than 1,000/microL; if the ANC was less than 1,000/microL, the dose of GM-CSF was increased to 3.0 micrograms/kg, and at 2-week intervals either zidovudine was restarted or the dose of GM-CSF was increased to 5 micrograms/kg and then 10 micrograms/kg, to maintain the ANC greater than 1,000/microL. Group B patients received full-dose zidovudine concurrently with GM-CSF administration. The dose of GM-CSF was increased every 2 weeks if necessary to keep the ANC greater than 1,000/microL while maintaining full-dose zidovudine therapy. Patients in each group showed an increase in total white blood cell (WBC) count. Neutrophils and eosinophils were responsible for the majority of this increase. Patients in group A had a more rapid increase in WBC than those in group B; however, by week 8, the WBC in each group was essentially equal. Viral replication as measured by human immunodeficiency virus (HIV) p24 antigen (Ag) was decreased in four patients in each group, increased in one patient in each group, and remained unchanged in the remainder. The ability to culture virus from peripheral blood mononuclear cells was not changed by the regimen. The major toxicities of the regimen were fever and malaise.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor ameliorates zidovudine-induced neutropenia in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex. 174 82

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

Levels of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in sera of 28 HIV-seronegative heterosexual non-intravenous drug using controls, 57 HIV-seronegative and 42 HIV-seropositive asymptomatic intravenous drug users (IVDU) and 36 HIV-seronegative and 36 HIV-seropositive homosexuals, 79 patients with lymphadenopathy, 11 patients with AIDS-related complex (ARC) and 110 patients with AIDS. Serum erythropoietin levels were significantly elevated in HIV-seronegative and HIV-seropositive asymptomatic homosexuals and in patients with lymphadenopathy, ARC and AIDS when compared to controls. However, in asymptomatic HIV-seronegative and HIV-seropositive IVDU the erythropoietin levels were not significantly different from the control group. GM-CSF mean levels in both HIV-seronegative and HIV-seropositive IVDU were elevated compared with the level in controls, whereas the mean levels in both the HIV-seronegative and HIV-seropositive homosexuals were decreased relative to the level in controls. GM-CSF levels in patients with lymphadenopathy, ARC and AIDS were not significantly different from the control value. It appears that male homosexuals have mildly increased erythropoietin levels which rise substantially with the development of ARC and AIDS, which suggests that AIDS patients have intact capacity to produce erythropoietin. In contrast, GM-CSF levels are increased in association with IVDU but are not increased in association with HIV infection including ARC or AIDS. The difference in circulating levels of erythropoietin and GM-CSF may reflect the tissue sources of erythropoietin predominantly in the kidney and GM-CSF being a product of the immunological and inflammatory systems.
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PMID:Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in sera of patients with HIV infection. 204 5

Patients may be intolerant of zidovudine for several reasons, the most prominent being hematologic toxicity. In vitro studies demonstrate that zidovudine is toxic to the myeloid and erythroid precursors in the bone marrow; at concentrations of zidovudine near those associated with the optimal antiviral effect in vitro, the proliferative capability of these progenitor cells is reduced 50%-70%. The clinical manifestations of anemia and leukopenia generally are time- and dose-dependent. Strategies for alleviating the hematologic toxicity of zidovudine include the use of hematopoietic growth factors, such as erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Myopathy, a recently recognized toxic effect of zidovudine, also appears to be time-dependent. Patients often complain of muscle weakness and discomfort and exhibit an associated elevation in creatine phosphokinase level; dose reduction or discontinuation of therapy generally is required. Some patients have experienced high fever, nausea, and vomiting; however, these effects are unusual and of unclear etiology. The substantial proportion of patients with AIDS or AIDS-related complex receiving zidovudine who experience hematologic or muscular toxicity may benefit from treatment with new antiviral agents, such as dideoxyinosine, with toxicity profiles different from that of zidovudine.
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PMID:Zidovudine intolerance. 220 Oct 71

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

In order to assess the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in the treatment of HIV-associated leukopenia, 35 subjects suffering from severe leukopenia/neutropenia (24 with a previous diagnosis of AIDS, 11 with AIDS-related complex), received rHuGM-CSF at 0.5-3 micrograms/Kg/day subcutaneously for a mean period of 9.7 +/- 12.5 weeks (range 2-43 weeks). Five patients have been treated continuously for more than 6 months. rHuGM-CSF administration led to a significant (at least two-fold; P < .001) increase in total leukocyte, neutrophil and monocyte count by the second week of treatment, subsequently maintained through the entire course of therapy. No considerable effects on other hematological, immunological and virological parameters have been detected. Patients treated with rHuGM-CSF did not suffer from novel opportunistic diseases, while bacterial infections occurred in only 3 cases (pneumonia in 2, otitis/mastoiditis in 1). Long-term treatment with rHuGM-CSF allowed continuation or resumption of potentially myelotoxic drugs in 22 patients out of 35. A self-limited flu-like syndrome represented the most common adverse event (observed in 15 patients), while no other significant clinical or laboratory abnormalities were found. In conclusion, long-term rHuGM-CSF therapy showed a good efficacy and safety profile in the treatment of HIV-related leukopenia, also increasing tolerability to potentially myelosuppressive drugs, and leading to a significant reduction in morbidity due to secondary infections.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in leukopenic patients with advanced HIV disease. 880 19