Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF) induced by Plasmodium berghei ANKA (PbA) infection was suggested to play an important role in the development of cerebral malaria (CM). We asked whether TNF-alpha/beta double-deficient mice, which have a complete disruption of the TNF-signaling pathways, are protected from CM and what might be the possible mechanisms of protection. PbA infection induces fatal CM in wild-type mice, which die within 5 to 8 days with severe neurological signs. In contrast, TNF-alpha/beta-deficient mice are completely resistant to PbA-induced CM. As PbA-induced up-regulation of endothelial intercellular adhesion molecule (ICAM)-1 expression as well as the systemic release of nitric oxide is found only in wild-type mice, TNF is apparently central for the recruitment of mononuclear cells and microvascular damage. Mononuclear cell adhesion to the endothelium, vascular leak and, perivascular hemorrhage are found only in the brain of wild-type mice. By contrast, the development of parasitemia and anemia is independent of TNF. Resistance to CM in TNF-alpha/beta-deficient mice is associated with reduced interferon-gamma and interleukin-12 expression in the brain, in the absence of increased T helper type 2 cytokines. In conclusion, TNF apparently is required for PbA-induced endothelial ICAM-1 up-regulation and subsequent microvascular pathology resulting in fatal CM. In the absence of TNF, ICAM-1 and nitric oxide up-regulation are reduced, and PbA infection fails to cause fatal CM.
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PMID:Resistance to cerebral malaria in tumor necrosis factor-alpha/beta-deficient mice is associated with a reduction of intercellular adhesion molecule-1 up-regulation and T helper type 1 response. 900 41

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r = -0.54; P < 0.001; sTNF-R II: r = -0.47; P < 0.001) as well as interleukin-6 levels (r = -0.29; P < 0.01). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II (P < 0.01). The results of this study suggest that similar to its action in vitro, activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-alpha, this activation is particularly reflected by elevations of soluble TNF receptor levels.
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PMID:Inadequate erythropoietin response to anaemia in HIV patients: relationship to serum levels of tumour necrosis factor-alpha, interleukin-6 and their soluble receptors. 902 5

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.
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PMID:[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction]. 905 65

Cardinal features of equine infectious anemia (EIA) include fever, hemolytic anemia and thrombocytopenia during the acute phase of the disease, and cachexia and anemia seen during the chronic phase. These signs are thought to result from the release of inflammatory cytokines such as TNF-alpha. In order to determine if TNF-alpha has a role in the pathogenesis of acute EIA and vaccine-induced disease enhancement, we measured plasma concentrations of TNF-alpha in ponies immunized with virus enriched major core protein-p26 and/or experimentally infected with EIAV. Naturally infected inapparent EIAV carriers were also studied. TNF-alpha levels were determined by means of a WEHI 164, clone 13 cytotoxicity assay. We show a significant positive temporal correlation between TNF-alpha levels, severity of symptoms (fever and thrombocytopenia) and viremia. Furthermore, TNF-alpha levels also correlate with strain virulence and the disease enhancement seen in vaccinated ponies. Of this group of animals, those challenged with a heterologous virulent strain presented the most unfavorable outcome as well as the highest levels of TNF-alpha and viremia. The TNF-alpha activity observed in the bioassay was completely abrogated by a polyclonal rabbit anti-human TNF-alpha antiserum, thus confirming the specificity of the plasma cytotoxicity. Our observations indicate that TNF-alpha production correlates with the outcome of infection with EIAV.
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PMID:Tumor necrosis factor-alpha production and disease severity after immunization with enriched major core protein (p26) and/or infection with equine infectious anemia virus. 923 36

Pregnant women, especially primigravidas, are highly susceptible to malaria infection, resulting in maternal anemia and low birth weight infants. Because circulating parasitemia is rare in the newborn, the cause of poor fetal outcomes has been unclear. We measured cytokine concentrations in placentas collected from women delivering in urban hospitals in malaria-holoendemic or nonendemic areas of Kenya. Normal placentas displayed a bias toward type 2 cytokines; type 1 cytokines IFN-gamma and IL-2 were absent in placentas not exposed to malaria but present in a large proportion of placentas from a holoendemic area. TNF-alpha and TGF-beta concentrations were significantly higher, and IL-10 concentrations significantly lower, in placentas from the holoendemic area. Among primigravidas, placental TNF-alpha concentrations were significantly higher in the presence of severe maternal anemia, and both IFN-gamma and TNF-alpha were significantly elevated when a low birth weight, rather than normal weight, infant was delivered. We conclude that maternal malaria decreases IL-10 concentrations and elicits IFN-gamma, IL-2, and TNF-alpha in the placenta, shifting the balance toward type 1 cytokines. This is the first demonstration that these placental cytokine changes are associated with poor pregnancy outcomes in humans.
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PMID:Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. 949 98

Lentiviruses replicate in cells of the immune system, and activation of immune cells has been shown to modulate virus replication. To determine the effects of macrophage activation on replication of equine infectious anaemia virus (EIAV), primary horse macrophage cultures (HMCs) were established from 20 different horses, infected with an avirulent strain of EIAV, and stimulated with 5 microg/ml of bacterial endotoxin. Supernatants collected from HMCs were assayed for the presence of tumour necrosis factor (TNF-alpha) and for production of infectious virus. Results indicated that EIAV replication in vitro varied significantly (P < or = 0.0001) from horse to horse, regardless of the treatment of HMCs. Also, EIAV replication was significantly (P < or = 0.0001) decreased in HMCs stimulated with bacterial endotoxin as compared to untreated HMCs. No significant correlation was found between virus replication and production of TNF-alpha following treatment of virus-infected cells with bacterial endotoxin. However, when HMCs were treated with endotoxin prior to virus infection, inhibition of EIAV replication was proportional to increasing levels of endotoxin. PCR and RT-PCR were used to amplify EIAV proviral DNA and mRNA sequences, respectively, at various time-points following infection. The results indicated that the early events of EIAV replication, up to and including transcription of multiple-spliced mRNAs, were not inhibited by treatment of EIAV-infected macrophages with bacterial endotoxin. This suggests that endotoxin treatment inhibits a posttranscriptional step in the virus replication cycle.
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PMID:Endotoxin treatment of equine infectious anaemia virus-infected horse macrophage cultures decreases production of infectious virus. 956 70

The levels of IL-1 alpha, IL-2, IL-6 and TNF-alpha were measured immunoradiometrically in the sera of 82 myelodysplastic (MDS) patients at diagnosis in an attempt to identify possible relationships between serum cytokine levels and clinical and laboratory parameters of the patients. We found that serum IL-6 and TNF-alpha concentrations were significantly higher in the group of MDS patients than in the normal controls (p < 0.03 and p < 0.001, respectively), while serum IL-1 alpha and IL-2 levels did not differ statistically between patients and control subjects. Elevated serum IL-6 and TNF-alpha concentrations were mainly seen in patients with high-risk myelodysplasia (MDS), i.e. patients with chronic myelomonocytic leukemia (CMML) (p < 0.05 and p < 0.001, respectively), refractor anemia with excess of blasts (RAEB) (p < 0.01 and p < 0.001, respectively), or refrochopy anemia with excess of blasts in transformation to acute leukemia (RAEB-t) (p < 0.001 and p < 0.001, respectively). Patients with low-risk disease, i.e. patients with refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS), had serum cytokine levels comparable to those of controls. Patients' serum IL-6 and TNF-alpha correlated inversely with the hemoglobin concentration (p < 0.01 and p < 0.05, respectively) and positively with the absolute number of circulating myeloblasts (p < 0.01 and p < 0.001, respectively) and the proportion of bone marrow (p < 0.001 and p < 0.001, respectively) myeloblasts. A negative correlation was also noted between serum TNF-alpha concentrations and patients' survival in high-risk MDS (p < 0.02). We concluded that elevated serum IL-6 and TNF-alpha values are seen mainly in patients with high-risk disease, and that high serum TNF-alpha concentrations are predictive of shortened survival in this group of patients.
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PMID:Elevated serum TNF-alpha concentrations are predictive of shortened survival in patients with high-risk myelodysplastic syndromes. 970 53

Apoptosis of haemopoietic cells in the marrow of patients with myelodysplastic syndrome (MDS) has been suggested as a mechanism for peripheral cytopenias. We determined the expression of Fas (CD95), Fas-Ligand (Fas-L) and TNF-alpha factors known to be involved in apoptosis, in the marrow of 44 patients with MDS and characterized their functional relevance in in vitro assays of haemopoiesis. Multidimensional flow cytometry revealed phenotypically aberrant blasts as defined by orthogonal light scatter and CD45 expression in the marrow of 24/44 patients. Among those blasts Fas expression was increased on CD34-positive cells and on cells co-expressing HLA-DR. In addition, Fas-L was expressed on some CD34+ cells of MDS patients but was never detected on CD34+ cells in normal marrow. Fas and Fas-L mRNAs as well as mRNA for TNF-alpha, known to increase Fas expression in normal marrow, were up-regulated in patients with MDS. TNF-alpha protein and sTNF-R1 levels in marrow plasma were higher in MDS patients than in controls (P<0.002 and <0.003, respectively). However, results were dependent upon disease category: TNF-alpha levels were significantly higher in patients with refractory anaemia (RA) than in patients with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-T) (P=0.043). Conversely, the proportion of Fas-L-positive cells was lowest in patients with RA (P=0.037). In marrow cultures, Fas-Ig, rhuTNFR:Fc or anti-TNF-alpha antibody, by blocking Fas or TNF mediated signals, respectively, significantly increased the numbers of haemopoietic colonies compared to untreated cells (P<0.001, P<0.003, P<0.001, respectively). These results show significant dysregulation in the expression of TNF-alpha, Fas and Fas-L in the marrow from MDS patients. Altered expression of these molecules appears to be of functional relevance in the dysregulation of haemopoiesis in MDS and may be amenable to therapeutic interventions.
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PMID:A role for tumour necrosis factor-alpha, Fas and Fas-Ligand in marrow failure associated with myelodysplastic syndrome. 979 6

We hypothesised that, in "anaemia of chronic disorders" (ACD), a local immune activation in the bone marrow alters erythropoiesis. We determined the activation status of bone marrow T-lymphocytes and the levels of cytokines. Patients (n = 27) with chronic inflammatory diseases and low hemoglobin values who had undergone bone marrow aspiration were divided into 2 groups according to the aetiology of anaemia: (1) unknown or (2) known causes (i.e. iron, folic acid and/or vitamin B12 deficiencies). Cytokines in peripheral blood and bone marrow serum were measured by ELISA and T-lymphocytes were phenotyped by flow cytometry. Peripheral blood from 27 age-matched healthy donors and bone marrow from 3 transplantation donors served as control. The erythrocyte count in the peripheral blood of patients with unknown aetiology of anaemia (group 1) was lower than in patients with known aetiology (group 2). This indicated that group 1 included most patients with ACD. Both groups had active disease, as shown by elevated levels of C-reactive protein and the erythrocyte sedimentation rate. The levels of IL-6 and IL-7 in the peripheral blood were higher in patients of group 1 than in patients of group 2 or normal subjects. The levels of IL-6, IL-7 and TNF-alpha in the bone marrow also were higher in group 1 compared to group 2. The CD4+ and CD8+ T-lymphocytes of the bone marrow showed a more activated phenotype than peripheral blood T-lymphocyte with the number of T-lymphocytes that expressed the early activation marker, CD69, being higher in group 1 than in group 2. A smaller proportion of "naive" cells (CD45RO-, CD69-) was accompanied by a higher proportion of "false naive" cells (CD45RO-, CD69+). In the bone marrow, elevated levels of IL-7 were correlated with fewer "naive" and more "false naive" cells in the CD4+ T-lymphocyte subpopulation. In group 1 only, a significant inverse relation was observed between the erythrocyte counts in blood and the levels of IL-7 in bone marrow. Thus, in patients with unknown aetiology of anaemia--a group including most patients with ACD-, an interrelationship may exist between the local activation of bone marrow T-lymphocytes, increased production of cytokines, and reduced erythropoiesis.
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PMID:Activation of CD4+ and CD8+ T-lymphocytes in bone marrow associated with reduced erythropoiesis in patients with chronic inflammation and anaemia. 982 95

The balance between Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma) and Th2 cytokines (interleukin [IL]-10, -4) may be critical in the development of severe falciparum malaria. Therefore, plasma concentrations of these cytokines were determined in children with various manifestations of malaria. Plasma levels of IFN-gamma and IL-4 were undetectable in most children. However, TNF-alpha and IL-10 were significantly elevated in children with high-density parasitemia and malaria anemia compared with children in control groups. In children with mild malaria, IL-10, but not TNF-alpha, was significantly elevated. While the highest concentrations of TNF-alpha were found in children with malaria anemia, IL-10 levels were highest in children with high-density uncomplicated malaria. The mean ratio of IL-10 to TNF-alpha was significantly higher in children with mild and high-density parasitemia (4.64, P<.005) than in children with malaria anemia (1.77). Thus, higher levels of IL-10 over TNF-alpha may prevent development of malaria anemia by controlling the excessive inflammatory activities of TNF-alpha.
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PMID:A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. 1051 52


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