Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haematopoiesis is regulated by unrelated, pleiotropic, and diverse regulatory molecules, cytokines, whose membrane receptors are related and restricted to a few families manifesting sequence homology. Most members of the cytokine receptor family which lack tyrosine kinase activity are composed of multiple chains. An accessory signal transducer can be shared by members of the receptor family. Cytokine receptor oligomerisation is required for signal transduction, which includes phosphorylation of receptors and cytoplasmic proteins. Upon ligand binding, the receptors for erythropoietin and G-CSF form homodimers, whereas other members of the receptor family form hetero-oligomers in order to generate high-affinity receptor and signal transduction. In their cytoplasmic part, cytokine receptors contain distinct functional domains, proximal and distal to the membrane, that generate separate signals. Cytokines can be used to minimise chemotherapy-induced neutropenia and treat chronic neutropenia, and to shorten the period of aplasia following bone marrow transplantation.
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PMID:[Hematopoiesis. Biological mass production closely regulated by cytokines]. 770 97

In patients with end-stage liver disease complicated with hypersplenism, neutropenia and thrombocytopenia are risk factors for systemic sepsis and spontaneous bleeding. Granulocyte-macrophage colony-stimulating factor is a naturally occurring cytokine that promotes proliferation and differentiation of granulocyte and monocyte progeny cells. In addition, it is reported to promote the proliferation of megakaryocytes. Its use as an intravenous infusion is Federal Drug Authority (USA) approved for the enhancement of myeloid recovery following autologous bone-marrow transplantation. The present study was initiated to determine whether granulocyte-macrophage colony-stimulating factor could be used to increase the white blood cell and platelet count in patients with cirrhosis and hypersplenism and to determine whether the more convenient subcutaneous route can be used with the same efficacy as the recommended intravenous route. Nine patients with cirrhosis and hypersplenism manifested by a reduced absolute neutrophil count (mean value of 1300 +/- 200/mm3) were studied. In eight patients, Indium white blood cell splenic sequestration scans were obtained before and after the administration of granulocyte-macrophage colony-stimulating factor intravenous infusion or subcutaneously for 7 days. One patient had to discontinue the therapy due to a reaction to granulocyte-macrophage colony-stimulating factor. Following intravenous infusion of granulocyte-macrophage colony-stimulating factor, the mean absolute neutrophil count increased to 2600 +/- 1100/mm3. Following subcutaneous administration, the mean absolute neutrophil count increased to 4100 +/- 200/mm3. No significant change in platelet count occurred with either route of administration. Indium scans obtained before and after the treatment period revealed no significant difference in the splenic uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of granulocyte-macrophage colony-stimulating factor to enhance hematologic parameters of patients with cirrhosis and hypersplenism. 781 5

The complication of secondary myelodysplastic syndrome (sMDS) during the course of multiple myeloma (MM) has been recognized for more than a decade. sMDS occurs years after MM diagnosis, and typically, at sMDS presentation the MM is stable or inactive. We report a 56-year-old patient, who developed sMDS 15 years following the diagnosis of IgG-lambda MM, which had been completely stable for 13 years. However, very soon after sMDS was diagnosed, the MM relapsed and required combination chemotherapy. The first cycle of vincristine, adriamycin and dexamethasone (VAD) resulted in severe neutropenia and sepsis, which was treated with antibiotics and recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Two weeks after GM-CSF administration a transformation to acute myeloblastic leukemia was observed. The relation between GM-CSF and the leukemic transformation is discussed and the possible contribution of the cytokine to the stimulation of this complication is emphasized.
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PMID:Is granulocyte-macrophage colony-stimulating factor (GM-CSF) safe in myelodysplastic syndromes? 789 Feb 61

Interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF) are important mediators of fever and inflammation, and are involved in the pathogenesis of sepsis. There is only limited data on serum concentrations of these proinflammatory cytokines in patients with fever and neutropenia, and their interrelationship and correlation with body temperature and clinical disease early in the febrile response during neutropenia have not been studied. Immunoreactive TNF, IL-1 beta, IL-6, and IL-8 in serum samples serially obtained from 14 adult patients with neutropenia and fever considered or documented to be due to infection were measured. IL-6 and Il-8 were consistently elevated in all patients, and correlated well with each other and with body temperature. Median peak concentration of IL-6 and IL-8 were 400 pg/ml (range: 100 to 41,000 pg/ml), and 1,025 pg/ml (range: 600 to 26,000 pg/ml), respectively, and levels of both cytokines rapidly declined in patients responding to antimicrobial therapy. Despite frequent sampling before and after the temperature peaks TNF and IL-1 beta, conversely, were less frequently detectable, with median peak values of < 10 pg/ml (range: < 10 to 150 pg/ml) for TNF, and 17 pg/ml (range: < 10 to 36 pg/ml) for IL-1 beta, respectively. The role of neutro- and monocytopenia with depletion of important cytokine producing and target cells in this particular cytokine response pattern needs to be further studied.
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PMID:Kinetics and correlation with body temperature of circulating interleukin-6, interleukin-8, tumor necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia. 792 10

Since the M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) regimen was reported by Sternberg in 1985, it has been widely accepted for the treatment of metastatic transitional cell carcinoma. This regimen has a significantly high response rate, but bone marrow suppression and gastrointestinal (GI) symptoms are inevitable. To complete this M-VAC regimen, preventive therapy for side effects is necessary. From November 1986 to March 1993, a total of 72 patients were admitted and received M-VAC therapy at our hospital. All of them had metastatic or invasive transitional cell carcinoma and they received a total of 163 complete courses of M-VAC therapy. We examined the side effects of this M-VAC regimen, and evaluated the effectiveness of colony-stimulating factor for prevention of granulocytopenia or granisetron for prevention of GI symptoms. Twenty-three patients (39 courses) were given recombinant colony-stimulating factor. This cytokine prevented the nadir of neutropenia and shortened the period to reach the nadir and period that the neutrophil count was below 1,000/mm3. Twelve patients (26 courses) were given granisetron, with significant reduction of the incidence of GI symptoms. These findings suggest that M-VAC therapy is effective and safe when used in combination with these drugs.
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PMID:[M-VAC chemotherapy for advanced urothelial cancer--side effects and their management]. 794 64

Sera of ten healthy controls and of 15 patients with myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) with a cell-free enzyme-linked immunosorbent assay (ELISA). The patients with MDS underwent treatment with IL-3: eight patients at dose levels of 250 and 500 micrograms/m2 s.c. daily for 15 days, and seven patients at the dose levels of 60 and 125 micrograms/m2 s.c. three times per week for 12 weeks. None of the patients had reported infectious episodes or been under treatment with cytotoxic drugs and/or cytokines within the preceding 2 months. sIL-2R levels were elevated in MDS patients compared with healthy controls (p < 0.001). sIL-2R increased in the high-dose treatment group from 504 +/- 68 U/ml to 731 +/- 199 U/ml (p < 0.025). The increased sIL-2R expression in MDS could be a primary event due to involvement of lymphocytes in the malignant clone or due to a secondary alteration of the cytokine network caused by chronic neutropenia. A down-regulation of the immune response caused by neutralization of free IL-2 by sIL-2R during IL-3 therapy seems possible.
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PMID:Induction of soluble IL-2 receptor in patients with myelodysplastic syndromes undergoing high-dose interleukin-3 treatment. 800 57

Previous reports have indicated that immunological priming of animals will result in increased cytokine production and enhanced susceptibility to the toxicity of cytokines. We primed mice with complete Freund's adjuvant and challenged 2 weeks later with 1 mg/mouse of lipopolysaccharide. Primed mice produced less tumor necrosis factor than naive mice (35 +/- 8 vs 108 +/- 20 ng/ml) and also less interleukin-6 (182 +/- 37 vs 6.39 +/- 155 ng/ml). Leukopenia developed only in the naive mice. Although neutropenia and lymphocytosis developed in both groups, the alterations manifested themselves more quickly in primed mice. Primed mice had substantially greater pulmonary neutrophil sequestration determined both enzymatically and histologically but no lung damage. However, primed mice had significantly less small bowel damage than naive mice. Mortality was substantially reduced in primed mice compared with unprimed mice. These results demonstrate that immunological priming in vivo decreases cytokine production in response to lipopolysaccharide challenge, decreases organ injury, and reduces mortality.
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PMID:Immunological priming attenuates the in vivo pathophysiological response to lipopolysaccharide. Comparison of cytokine production, tissue injury, and lethality in complete Freund's adjuvant-primed mice and in unprimed mice. 812 45

Pulmonary dysfunction caused by pulmonary neutrophil sequestration is a frequent postoperative complication in patients undergoing cardiopulmonary bypass (CPB) surgery. It is yet unclear whether treatment with corticosteroids in vivo in these patients can prevent complement-mediated neutrophil activation and sequestration in the lungs. Therefore, we conducted a prospective study in order to investigate whether methylprednisolone (MP) pretreatment (30 mg/kg) could influence the appearance of IL-8 (a recently discovered cytokine with potent neutrophil-chemotactic activity) in the peripheral circulation. We also studied the effects of MP pretreatment on the inflammatory parameters in the bronchoalveolar lavage (BAL) fluid 4 h postoperatively. Although peripheral neutropenia and the rise in IL-8 serum levels was less pronounced in MP-treated than in non-steroid-treated patients, there was no significant difference in albumin, total protein, concentrations of IL-8 and C3a, and the number of neutrophils in the BAL fluid between the two groups. However, when cultured in vitro, alveolar macrophages from patients treated with MP released significantly lower IL-8, both in basal conditions and after stimulation with lipopolysaccharide. Our results show that MP does not prevent (IL-8-mediated) pulmonary neutrophil infiltration after CPB, although it might affect certain aspects of the microvascular lung injury.
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PMID:Interleukin-8 production in patients undergoing cardiopulmonary bypass. The influence of pretreatment with methylprednisolone. 821 44

Single cytokine therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) has been shown to be effective in decreasing the respective periods of neutropenia and thrombocytopenia following radiation- or drug-induced marrow aplasia. The combined administration of IL-3 and GM-CSF in normal primates suggested that a sequential protocol of IL-3 followed by GM-CSF would be more effective than that of GM-CSF alone in producing neutrophils (PMN). We investigated the therapeutic efficacy of two combination protocols, the sequential and coadministration of recombinant human IL-3 and GM-CSF relative to respective single cytokine therapy, and delayed GM-CSF administration in sublethally irradiated rhesus monkeys. Monkeys irradiated with 450 cGy (mixed fission neutron:gamma radiation) received either IL-3, GM-CSF, human serum albumin (HSA), or IL-3 coadministered with GM-CSF for days 1 through 21 consecutively postexposure, or IL-3 or HSA for days 1 through 7 followed by GM-CSF for days 7 through 21. All cytokines and HSA were injected subcutaneously at a total dose of 25 micrograms/kg/d, divided twice daily. Complete blood counts (CBC) and platelet (PLT) counts were monitored over 60 days postirradiation. The respiratory burst activity of the PMN was assessed flow cytometrically, by measuring hydrogen peroxide (H2O2) production. Coadministration of IL-3 and GM-CSF reduced the average 16-day period of neutropenia and antibiotic support in the control animals to 6 days (P = .006). Similarly, the average 10-day period of severe thrombocytopenia, which necessitated PLT transfusion in the control animals, was reduced to 3 days when IL-3 and GM-CSF were coadministered (P = .004). The sequential administration of IL-3 followed by GM-CSF had no greater effect on PMN production than GM-CSF alone and was less effective than IL-3 alone in reducing thrombocytopenia. PMN function was enhanced in all cytokine-treated animals.
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PMID:Combination protocols of cytokine therapy with interleukin-3 and granulocyte-macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia. 821 92

This report describes a patient with combined immune deficiency associated with congenital neutropenia (CID/CN) and reports a partial characterization of his hematopoietic abnormalities. The CID/CN syndrome described is characterized by neutropenia and by deficiencies in B-lymphoid and T-lymphoid cell number and function. Red cell and platelet counts were normal. In vitro assays indicate that the myeloid lineage was developmentally arrested at the level of the committed monocyte/granulocyte progenitor (CFU-GM), while precursors to the CFU-GM progenitor were normal. In vitro studies showed that the defect in myeloid development was not corrected with G-CSF or GM-CSF. However, combinations of cytokines present in conditioned media from the T-cell lines MO or C5MJ, or defined multiple cytokine combinations containing IL-1, IL-3, GM-CSF, kit ligand, IL-6, and IL-9, restored myelopoiesis in-vitro. In contrast, C5MJ-conditioned media did not correct deficiencies in immune function in the patient's lymphocytes and accessory cells. No abnormalities in the production of G-CSF, GM-CSF, M-CSF, or IL-1 from the patient could be identified to account for the defects in myelopoiesis orimmune function.
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PMID:Dyshematopoiesis in combined immune deficiency with congenital neutropenia. 825 11


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