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)

RhGM-CSF is a hematopoietic growth factor which stimulates the proliferation, differentiation and functional activity of neutrophils, monocytes and macrophages. It also stimulates proliferation of endothelial cells and induces the production of other cytokines, such as interleukin (IL-1), tumor necrosis factor (TNF), interferon, prostaglandin E2, and plasminogen activating factor which affects both hematopoietic and non-hematopoietic cell activities. Initial clinical studies in 1987 generally excluded experimental therapy with rhGM-CSF in pediatric patients (age < or = 17 years) unless life threatening illness related to neutropenia and infection developed (i.e., patients with graft failure). Serious complications of patients undergoing autologous bone marrow transplantation (BMT) related to pancytopenia include infection and hemorrhage. Other regimen related complications include venooclusive disease, pneumonitis and mucositis. As a result of these complications, patients require intensive medical support including antibiotics and hyperalimentation. Initial hospital duration following marrow reinfusion is generally 4 to 5 weeks. Hematopoietic growth factors have been administered to patients undergoing autologous BMT as an attempt to reduce regimen related toxicity.
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PMID:RhGM-CSF in bone marrow transplantation: experience in pediatric patients. 130 85

The antiviral drug used in the treatment of acquired immunodeficiency syndrome, zidovudine, has proved effective in ameliorating the morbidity and mortality associated with human immunodeficiency virus infection. However, associated with zidovudine is the development of severe bone marrow toxicity manifested by anemia, neutropenia, and occasionally thrombocytopenia. We report the results of studies that demonstrate the ability of basic fibroblast growth factor (B-FGF) to reduce zidovudine toxicity to several classes of hematopoietic progenitors (granulocyte-macrophage, CFU-GM; megakaryocyte. CFU-Meg; and erythroid, BFU-E) from normal murine, human, and murine retrovirus-infected bone marrow cells when cocultured with zidovudine in vitro. Optimal response to B-FGF was observed at a dose concentration of 10 ng/ml. The specificity of B-FGF was demonstrated in the presence of protamine sulfate, an effective inhibitor of B-FGF mitogenic activity. In addition, synergistic activity of B-FGF on zidovudine-induced hematopoietic stem cell toxicity was observed in the presence of interleukin 1 (IL-1) (30 ng/ml). These studies demonstrate that B-FGF is capable of reducing the hematopoietic toxicity associated with zidovudine and that such an effect can be amplified in the presence of IL-1.
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PMID:In vitro modulation of the toxicity associated with the use of zidovudine on normal murine, human, and murine retrovirus-infected hematopoietic progenitor stem cells with basic fibroblast growth factor and synergistic activity with interleukin-1. 131 78

To evaluate the clinical effect by administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy in non-Hodgkin malignant lymphoma (NHL), 17 patients with NHL were subjected to this study. Administration of rhG-CSF ameliorated the decrease in absolute neutrophil counts after the cytotoxic chemotherapies and activated neutrophil functions in active oxygen product and expressions of adhesion proteins. To consistent with these results, rhG-CSF administrations post cytotoxic chemotherapy were effective for reducing infection complications associated with neutropenia. Furthermore, administration of rhG-CSF increased peripheral hematopoietic progenitor cells, thus suggesting promising therapeutic potential for autografting. Recently, it has been reported that blood neutrophils may synthesize mRNA and proteins important in inflammation including various cytokines such as IL-1, IL-6, TNF-alpha and IFN-alpha, but, administration of rhG-CSF showed no obvious effect on the level of either IL-1, IL-6, TNF-alpha or IFN-alpha in sera, and furthermore, the in vitro stimulation by rhG-CSF induced no significant production of these cytokines and expressions of TNF-alpha and IFN-alpha mRNAs. Finally, we studied on anti-tumor effect of administration of rhG-CSF in CDF1 mice inoculated with syngeneic lymphoma cells. rhG-CSF infusion suppressed the liver metastasis and prolonged the overall survival, thus suggesting the hypothesis that use of rhG-CSF in some patients with NHL might control the disease through stimulating both production and functional activation of neutrophils.
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PMID:[In vivo effects on human neutrophils by administration of rhG-CSF and clinical significance]. 137 67

The present study demonstrates that CSA is capable of inhibiting indomethacin-induced leukocyte adherence to the vascular endothelium, and can reduce the severity of indomethacin-induced gastric mucosal injury. These results are therefore consistent with the hypothesis that leukocyte (particularly neutrophil) adherence is a critical event in the pathogenesis of NSAID-induced gastropathy. The mechanism through which CSA inhibits leukocyte adherence is not clear, and warrants further investigation. This study also confirmed the protective effects of IL-1 in experimental NSAID-gastropathy, and demonstrates that one of the ways the IL-1 may protect the mucosa is through its ability to inhibit the release of proinflammatory mediators (e.g., PAF) and promote the release of antiinflammatory mediators (e.g., nitric oxide). IL-1 modulated the release of these mediators from peritoneal mast cells at doses in the pg/ml to ng/ml range. IL-1 can inhibit the ability of neutrophils to respond to chemotactic stimuli and can prevent LTB4-induced neutropenia. Inhibition of neutrophil function by IL-1 may therefore account for its ability to reduce NSAID-induced gastric mucosal injury. Whether or not effects of IL-1 on the production of mediators such as nitric oxide and PAF is an underlying mechanism for the inhibitory effects on neutrophil function remains to be determined.
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PMID:Immunopathology of NSAID-gastropathy: inhibitory effects of interleukin-I and cyclosporin A. 145 66

The ability of highly purified, recombinant human macrophage colony-stimulating factor (M-CSF) and recombinant human interleukin 1 alpha (IL-1) to rescue hematopoietic activity from the myelosuppressive effects of 5-fluorouracil (5-FU) was investigated in the C57Bl/6 mouse. IL-1 (q24 h x 4) stimulated granulopoietic recovery in the 5-FU-treated animals and reduced the period of severe neutropenia associated with this drug by 7 days. Chronic M-CSF administration (q24 h x 14), on the other hand, resulted in a modest retardation of granulocyte recovery, and, when combined with IL-1, the chronic administration of M-CSF significantly dampened the accelerated recovery of granulopoietic activity observed with IL-1 alone. Consistent with their effects on neutrophil recovery, IL-1 alone markedly enhanced the recovery of the granulocyte erythrocyte macrophage megakaryocyte colony-forming units (CFU-GEMM), macrophage colony-forming units (CFU-M), and erythroid burst-forming units (BFUe) in the marrow, whereas M-CSF failed to demonstrate a significant influence on the restoration of these hematopoietic progenitors (with the exception of delaying the recovery of the BFUe). Unexpectedly, the combination of IL-1 plus M-CSF (q24 h, days 1-4) followed by M-CSF (q24 h, days 5-14) resulted in a more than additive stimulation of progenitor recovery in both the marrow and the spleen that was observed as early as day 3 following 5-FU treatment. Furthermore, in the absence of protracted M-CSF administration on days 5-14, the 4-day rescue with a combination of IL-1 plus M-CSF also resulted in a more than additive effect on the recovery from 5-FU-induced neutropenia. Collectively, these observations demonstrated that IL-1 and M-CSF can interact synergistically to stimulate granulopoietic recovery in the 5-FU-treated animal. However, the data also suggest that the continued administration of M-CSF following the 4-day IL-1 plus M-CSF rescue may interfere with the restoration of neutrophils in the myelosuppressed animal.
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PMID:Synergy between recombinant human IL-1 alpha (rHuIL-1) and M-CSF (rHuM-CSF) during the recovery of murine hematopoietic activity in myelosuppressed animals: abbreviated versus chronic administration of rHuM-CSF. 158 5

A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils.
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PMID:Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. 190 12

The diversity of infectious agents capable of inducing meningitis and blood-brain barrier (BBB) injury suggests the potential for a common host mediator. The inflammatory polypeptides, IL-1 and TNF, were tested in an experimental rat model as candidate mediators for induction of meningitis and BBB injury. Intracisternal challenge of rIL-1 beta into rats induced neutrophil emigration into cerebrospinal fluid (CSF) and significantly increased BBB permeability to systemically administered 125I-BSA as early as 3 h later (P less than 0.05). This injury was reversible, dose dependent and significantly inhibited by prior induction of systemic neutropenia (via intraperitoneal cyclophosphamide) or preincubation of the rIL-1 beta inoculum (50 U) with an IgG monoclonal antibody to rIL-1 beta. Similar kinetics and reversibility of CSF inflammation and BSA permeability were observed using equivalent dose inocula of rIL-1 alpha. rTNF-alpha was less effective as an independent inducer of meningitis or BBB injury over an inoculum range of 10(1) U (0.0016 micrograms/kg)-10(6) U (160 micrograms/kg) when injected intracisternally, but inoculum combinations of low concentrations of rTNF alpha (10(3) U) and rIL-1 beta (0.0005-5.0 U) were synergistic in inducing both meningitis and BBB permeability to systemic 125I-BSA. These data suggest that in situ generation of interleukin-1 within CSF (with or without TNF) is capable of mediating both meningeal inflammation and BBB injury seen in various central nervous system infections.
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PMID:Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. 201 May 49

Recently it has been recognized that IL-1 plays an important role in hematopoietic regulation. Administration of 5-fluorouracil (5-FU) to mice causes prolonged neutropenia. rHIL-1 injected to mice after 5-FU, accelerated the recovery of hematopoietic progenitors and blood neutrophils. The combination of rhIL-1 and rhG-CSF reduced the neutropenic period significantly. Sublethal irradiation of mice induced profound neutropenia for 3 weeks which was associated with 80% mortality. Administration of rhIL-1 20 hours prior to or 2 hours post irradiation resulted in a significantly improved survival and rapid recovery of the neutrophil count. IL-1 administered alone or in combination with other colony stimulating factors to spontaneous breast tumor bearing mice following 5-FU therapy resulted in a rapid recovery of neutrophils, improved survival, and markedly reduced the tumor mass. Experiments in primates demonstrated that rhIL-1 administered to 5-FU treated animals shortened the neutropenic period from 30 to 17 days and increased the number of marrow progenitors responsive to other CSFs. Prolonged administration of IL-1 (14 days) to these animals resulted in a delayed neutrophil recovery as compared to animals receiving short courses of IL-1. rhIL-1 administered to primates receiving marrow grafts after lethal irradiation, did not result in rapid hematopoietic recovery. In humans, studies with CD-34 positive marrow cells showed that IL-1 had a radioprotective effect on a committed and early marrow progenitors. These data show the therapeutic potential of IL-1 in the treatment of chemoradiotherapy induced myelosuppression.
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PMID:Effects of IL-1 on hematopoietic progenitors after myelosuppressive chemoradiotherapy. 248 6

The beneficial effects of IL-1 and other cytokines on hematopoiesis and on resistance to infection are profound. IL-1 stimulates proliferation of bone marrow cells in normal mice and potentiates the recovery of peripheral blood neutrophils in mice with drug-induced neutropenia. Prophylactic cytokine administration provides an elevated level of natural resistance to infections which is correlated with increased numbers of phagocytic leukocytes. These studies suggest that IL-1 has potential clinical application as a therapy to limit bone marrow dysfunction and immunosuppression and to augment hematopoiesis and natural immunity. Further research will continue to elucidate the mechanisms whereby interleukins and colony-stimulating factors act, and interact, to promote restoration of leukocyte production and to enhance host resistance.
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PMID:Stimulation of hematopoiesis and antibacterial resistance by interleukin-1. 270 47

Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the second peak was as great as the initial peak of neutrophilia, supporting the hypothesis that the second peak of TNF-induced neutrophilia is due to the release of endogenous monokines. In conclusion, exogenous TNF, IL-1, and adrenal hormones affect circulating numbers of lymphocytes and neutrophils in a fashion consistent with their postulated endogenous role in the regulation of leukocyte trafficking during bacterial infection.
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PMID:Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats. 278 48


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