UMLS:C0027947 - FACTA Search

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Query: UMLS:C0027947 (neutropenia)
17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of inflammatory cytokines and chemokines were measured in 132 patients with chronic idiopathic neutropenia of adults (CINA) and 34 healthy volunteers (controls) using commercially available micro-ELISA determination kits. We found that serum interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), transforming growth factor-beta(1) (TGF-beta(1)), and soluble tumor necrosis factor receptor p55 (sTNF-RI) were all significantly increased in CINA patients compared to controls. Individual cytokine values inversely correlated with the number of circulating neutrophils. Serum levels of interleukin-8 (IL-8) and RANTES, two potent chemokines for neutrophils and lymphocytes, respectively, were also significantly increased in the group of patients and they inversely correlated with the number of circulating neutrophils. Contrarily, serum levels of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), soluble CD23 (sCD23), and soluble interleukin-2 receptor (sIL-2R) did not show any significant change in the patients studied. We assume that CINA patients have increased serum concentrations of inflammatory cytokines and chemokines mainly produced by activated macrophages, while they disclose normal levels of inflammatory molecules mainly released from activated lymphocytes. These findings provide further evidence for an underlying low-grade chronic inflammatory process in CINA patients, as we previously have suggested. If this chronic inflammation is really the cause of the disorder or it simply represents the result of neutropenia remains to be elucidated.
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PMID:Patients with chronic idiopathic neutropenia of adults have increased serum concentrations of inflammatory cytokines and chemokines. 1107 51

Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.
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PMID:Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury. 1107 4

A multicenter, double-blind, randomized, placebo-controlled study was conducted to determine the safety and efficacy of thalidomide in reduced, intermittent doses for preventing recurrences of oral and esophageal aphthous ulcers in patients with human immunodeficiency virus (HIV) infection. Forty-nine HIV-infected patients whose ulcers previously had healed as a result of thalidomide therapy were randomly assigned to receive either 100 mg of oral thalidomide or placebo 3 times per week for 6 months. Ulcers recurred in 14 (61%) of 23 thalidomide-randomized patients, compared with 11 (42%) of 26 placebo-randomized patients, with no significant difference in the median time to recurrence of ulcers (P=.221). There were no changes in plasma levels of HIV RNA, tumor necrosis factor (TNF)-alpha, and soluble TNF receptor II at the time of ulcer recurrence. Adverse events among patients treated with thalidomide included neutropenia (5 patients), rash (5 patients), and peripheral sensory neuropathy (3 patients). Thalidomide in lower intermittent doses is ineffective at preventing recurrence of aphthous ulcers in HIV-infected persons.
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PMID:Thalidomide in low intermittent doses does not prevent recurrence of human immunodeficiency virus-associated aphthous ulcers. 1112 Sep 35

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is used to ameliorate neutropenia in patients after antineoplastic treatment. It has also been suggested as an adjunct treatment in septic patients; however, the recruitment and priming of leukocytes by GM-CSF bears the hazard of a hyperinflammatory response. In particular, the role of GM-CSF in pulmonary functions in septic lungs is still unclear. Therefore, we pretreated rats in vivo with GM-CSF (50 microg/kg, intravenous) and assessed the pulmonary functions of their subsequently prepared isolated perfused lungs when exposed to subtoxic concentrations of lipopolysaccharide (LPS, 2 microg/ml). These lungs showed enhanced expression of cyclooxygenase 2 (COX-2), a significant increase in thromboxane (TX) and tumor necrosis factor (TNF) release into the venous perfusate, and bronchoconstriction. COX-2 inhibition or blocking of the TX receptor abolished the GM-CSF/LPS-induced bronchoconstriction, but not the TNF release. Neutralizing antibodies against TNF did not prevent GM-CSF/LPS-induced bronchoconstriction. After GM-CSF pretreatment, massive neutrophil invasion into the lung occurred. Neutropenic rats were protected against GM-CSF/ LPS-induced lung injury. Similar results were obtained in rats pretreated with G-CSF instead of GM-CSF. We conclude that GM-CSF pretreatment exacerbates pulmonary injury by low-dose LPS via COX-2 expression, TX release, and bronchoconstriction by initiating neutrophil invasion and activation.
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PMID:Granulocyte-macrophage colony-stimulating factor amplifies lipopolysaccharide-induced bronchoconstriction by a neutrophil- and cyclooxygenase 2-dependent mechanism. 1117 20

This study describes the frequency and the type of anemia seen in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). We found that NI-CINA patients had low hemoglobin levels and increased serum concentrations of erythropoietin (EPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). The hemoglobin levels correlated positively with the number of circulating neutrophils and inversely with the levels of EPO and TNF-alpha but not of IL-1beta. Anemia, defined as the reduction of the hemoglobin below 12.0 g/dl for women and 13.3 g/dl for men, was found in 23 out of 148 patients studied, a proportion of 15.5%. Two of the anemic patients had iron deficiency anemia (8.7%), 11 had anemia of chronic disease (ACD; 47.8%) presenting with normal or slightly reduced erythrocytic indices, low serum iron, and increased serum ferritin, and the remaining ten had anemia of undefined pathogenesis (AUP; 43.5%) with normal or slightly decreased erythrocytic indices, serum iron ranging from 43 to 88 microg/dl, and ferritin values ranging from 12 to 50 ng/ml. We conclude that ACD is the more frequent type of anemia seen in patients with NI-CINA, and that pro-inflammatory cytokines, notably TNF-alpha, may be involved in the pathogenesis of both ACD and AUP, given that serum levels of the cytokine were significantly increased and that the EPO response to anemia was blunted in these patients. These findings further support our previously reported suggestion for the possible existence, in NI-CINA patients, of an unrecognized low-grade chronic inflammatory process that may be involved in the pathogenesis of the disorder.
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PMID:Anemia of chronic disease is the more frequent type of anemia seen in patients with chronic idiopathic neutropenia of adults. 1140 Oct 84

There is strong evidence that non-immune chronic idiopathic neutropenia of adult is a cytokine-mediated syndrome characterized by (a) neutropenia of varying degree associated with a low number of lineage-specific CD34+ cells and increased production of inhibitors of hematopoiesis, including transforming growth factor-beta1 and tumor necrosis factor-alpha; (b) lymphopenia due to selective loss of primed/memory T-cells and NK cells; (c) increased splenic volume on ultrasonography in 48.1% of patients; (d) osteopenia and/or osteoporosis in 60.0% of patients; (e) anemia, mostly of the type of anemia of chronic disease, in 15.6% of patients; (f) features of chronic antigenic stimulation, including increased proportion of bone marrow plasma cells, increased serum levels of IgG1 and/or IgA, increased frequency of monoclonal gammopathy of undetermined significance, increased frequency of antinuclear antibodies with specific reactivity, and increased serum levels of circulating immune complexes; and (g) increased concentrations of a variety of macrophage-derived pro-inflammatory cytokines and chemokines capable of affecting bone metabolism, bone marrow function, and leukocyte trafficking. All these findings are suggestive of the existence of an unrecognized low-grade chronic inflammatory process which may be involved in the pathogenesis of the disorder. Neutropenia in these patients is probably the result of a combination of at least three factors, reduced neutrophil production in bone marrow, enhanced neutrophil extravasation, and increased sequestration and/or extravasation of neutrophils into the spleen.
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PMID:Non-immune chronic idiopathic neutropenia of adult: an overview. 1155 65

In this study, we explored a novel function of polymorphonuclear neutrophils (PMN) NAD(P)H oxidase in the mechanism of tumor necrosis factor-alpha (TNFalpha)-induced NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. Studies were made in mice lacking the p47(phox) subunit of NAD(P)H oxidase as well as in cultured mouse lung vascular endothelial cells (MLVEC) from these mice. In response to TNFalpha challenge, NF-kappaB activation and ICAM-1 expression were significantly attenuated in lungs of p47(phox)(-/-) mice as compared with wild-type (WT) mice. The attenuated NF-kappaB activation in p47(phox)(-/-) mice was secondary to inhibition of NIK activity and subsequent IkappaBalpha degradation. Induction of neutropenia using anti-PMN serum prevented the initial TNFalpha-induced NF-kappaB activation and ICAM-1 expression in WT mice, indicating the involvement of PMN NAD(P)H oxidase in signaling these responses. Moreover, the responses were restored upon repletion with PMN obtained from WT mice but not with PMN from p47(phox)(-/-) mice. These findings were recapitulated in MLVEC co-cultured with PMN, suggesting that NF-kappaB activation and resultant ICAM-1 expression in endothelial cells occurred secondary to oxidants generated by the PMN NAD(P)H oxidase complex. The functional relevance of the PMN NAD(P)H oxidase in mediating TNFalpha-induced ICAM-1-dependent endothelial adhesivity was evident by markedly reduced adhesion of p47(phox)(-/-) PMN in co-culture experiments. Thus, oxidant signaling by the PMN NAD(P)H oxidase complex is an important determinant of TNFalpha-induced NF-kappaB activation and ICAM-1 expression in endothelial cells.
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PMID:Role of neutrophil NADPH oxidase in the mechanism of tumor necrosis factor-alpha -induced NF-kappa B activation and intercellular adhesion molecule-1 expression in endothelial cells. 1172

Serum levels of interleukin-1 beta (IL-1beta), soluble interleukin 2 receptors (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) were measured to predict some characteristics of febrile episodes in children with cancer and neutropenia. Forty-eight episodes of febrile neutropenia were determined in 23 pediatric cancer patients, including 35 febrile episodes without identifiable source, 7 episodes of bacteremia due to Gram-negative organisms and 4 due to Gram-positive organisms, and 2 fungal infections. Interleukin-6, sIL-2R, and IL-8 levels were significantly higher at the beginning of the febrile episodes than those of controls (p < 0.001, p < 0.001, and p < 0.001). Interleukin-6, slL-2R, and IL-8 levels were higher in patients with bacteremia due to Gram-negative organisms than in those with Gram-positive ones (p = 0.042, p = 0.006, and p = 0.023, respectively). TNF-alpha and IL-1beta levels were similar in febrile episodes and controls (p > 0.05). In conclusion, sIL-2R, IL-6, and IL-8 levels may be helpful in the prediction of infection in febrile cancer patients with neutropenia and measurements of IL-1beta and TNF-alpha were not useful for identifying the presence and the type of infection in febrile neutropenic episodes in children.
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PMID:Serum levels of IL-1 beta, sIL-2R, IL-6, IL-8, and TNF-alpha in febrile children with cancer and neutropenia. 1177 70

Neutrophil (polymorphonuclear leukocyte [PMN]) migration into pulmonary airspaces is a prerequisite for clearance of bacteria commonly found in nosocomial pneumonia. Patients at risk for nosocomial pneumonia often experience endotoxemia, and neutrophil dysfunction is associated with endotoxemia in both humans and animals. Using a rodent model of endotoxemia-associated pneumonia, we characterized the altered kinetics of pulmonary PMN trafficking and addressed the roles of platelets, tumor necrosis factor (TNF), and products of complement activation as potential mediators in the modulation of PMN migratory function. In male Sprague-Dawley rats made endotoxemic with intravenously (i.v.) administered endotoxin (lipopolysaccharide [LPS]), recruitment of PMNs into the lung airspaces in response to intratracheally (i.t.) instilled LPS was inhibited. In animals given IT LPS alone (0.5 mg/rat), numbers of airway PMNs were significantly elevated by 2 h, and immunohistochemical evaluation revealed PMNs in alveolar airspaces, alveolar walls, and in interstitium surrounding large airways. LPS (2 mg/kg i.v.) caused neutropenia and pulmonary PMN sequestration within 15 min of administration. Inhibition of airway PMN accumulation occurred by 30 min and lasted for at least 6 h after i.v. LPS. Factors present or activated after 30 min of endotoxemia were hypothesized to mediate the inhibitory effect of i.v. LPS. We found that pretreatment of rats with cobra venom factor to deplete complement (and C5a production) or immunodepletion of platelets or TNF did not affect the ability of i.v. LPS to inhibit pulmonary PMN recruitment or to cause pulmonary leukostasis. In summary, our results show that the inhibitory effects of i.v. LPS on PMN trafficking are rapid and persist for several hours and suggest that neither TNF, C5a, nor platelets are sufficient to mediate the inhibitory response.
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PMID:Pulmonary leukostasis and the inhibition of airway neutrophil recruitment are early events in the endotoxemic rat. 1183 92

Hypocholesterolemia, which often accompanies infectious diseases has been suggested to serve as a prognostic marker in hospitalized patients. Even though patients with chemotherapy-induced leukopenia are at high risk of infection and mortality, only limited information is available on serum cholesterol levels in these patients. We therefore measured serum cholesterol levels in 17 patients with hematological malignancies during chemotherapy-induced neutropenia and correlated it with clinical outcome. Patients with fever (>38.5 degrees C) showed a significant decrease in serum cholesterol levels within 24 hours. Eight days after onset of the fever non-survivors had significantly lower serum cholesterol levels (median 2.09 mmol/l, range 0.49-2.79, n=6) compared to survivors (median 3.23 mmol/l, range 1.68-4.86, n=11). Cholesterol levels in survivors returned to baseline levels at the time of discharge from the hospital. At the onset of fever, serum levels of inflammatory cytokines interleukin-6, tumor necrosis factor (TNF) and soluble TNF receptors p55 and p75 were elevated in all patients, but only TNF and TNF receptor p75 levels were significantly different in survivors and non-survivors. Our data suggest that a decrease in serum cholesterol levels is a prognostic marker in neutropenic patients with fever. Release of inflammatory cytokines may in part be responsible for hypocholesterolemia in these patients.
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PMID:Serum cholesterol levels in neutropenic patients with fever. 1200 22

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