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)

Although the etiology of inflammatory bowel disease (IBD) is unknown, there is increasing evidence for the pivotal role played by tumor necrosis factor-alpha (TNF-alpha). Recent work has shown an increased concentration of TNF-alpha in both the bowel wall and in the stools of patients with IBD, and in children with that disease there are increased serum levels. Coincidental studies have shown that IL-10 knockout mice have increased levels of TNF-alpha and are known to develop a syndrome of stunted growth, anemia, bloody diarrhea, and colon tumors that mimics IBD. By injecting monoclonal antibodies intraperitoneally into IL-10 knockout mice, we were able to demonstrate significant histologic improvement of inflammation that correlates well with a resolution of diarrhea and rectal bleeding. This finding is consistent with a role for anti-TNF-alpha in the pathogenesis of IBD and suggests that this model may be of use for examining the effects of anti-TNF-alpha antibody administration.
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PMID:Murine monoclonal anti-tNF antibody administration has a beneficial effect on inflammatory bowel disease that develops in IL-10 knockout mice. 1218 21

Serum levels of tumor necrosis factor-alpha (TNF-alpha) and of erythropoietin (Epo) have been evaluated in 100 patients with B-cell chronic lymphocytic leukemia (CLL) in order to determine whether these factors could be significant in the development of anemia, which was observed in some cases with advanced disease. In our series of patients, TNF-alpha serum levels had an inverse correlation with hemoglobin levels (r = -0.813). In patients with anemia, the serum levels of TNF-alpha were significantly higher (p = 0.022) than in those without anemia (186.7 +/- 84.7 vs. 39.8 +/- 20.7 pg/ml). Serum Epo levels were also significantly (p = 0.0003) increased in CLL patients with anemia compared to those without (134.1 +/- 225.9 vs. 12.3 +/- 4.8 mU/ml). The ratio of observed/predicted (O/P) serum Epo was adequate (>0.8) for the degree of anemia in 70% of patients with anemia and inadequate in the remaining 30%. In the latter, the mean serum TNF-alpha level was significantly higher (p = 0.005) than the mean for the anemic cases with an adequate O/P ratio of serum Epo (234.1 vs. 166.4 pg/ml). These data suggest that although CLL anemia is not characterized by inadequate Epo production, in some CLL patients this factor may be correlated. In these cases, the levels of TNF-alpha were significantly higher than in other anemic cases. Compared to other CLL patients with anemia, these CLL patients might better respond to therapy with recombinant human Epo in pharmacological doses.
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PMID:Evaluation of tumor necrosis factor-alpha and erythropoietin serum levels in B-cell chronic lymphocytic leukemia patients with anemia. 1218 26

Thirty two patients of malaria (15, 11 & 6) having P. vivax, uncomplicated and complicated P. falciparum malaria respectively, and 10 healthy controls were subjected to full clinical and laboratory examinations as well as estimation of plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6) and nitric oxide (NO). The main clinical presentations were fever, pallor, jaundice, splenomegaly and anaemia which were more pronounced in patients with complicated falciparum malaria. Light coma (50%), convulsions (33.3%), severe anaemia (66.6%). severe hypoglycemia (66.6%) and increased blood lactate levels (50%) were detected in patients with complicated falciparum malaria. The results showed significant elevation of plasma levels of TNF, IL-6 and NO in all malaria patients as compared to the controls. The levels were significantly higher in patients with complicated falciparum malaria than in the other patient groups. The TNF, IL-6 and NO had an effective role in pathogenesis of malaria and their levels in can be a useful diagnostic markers for malaria and severity.
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PMID:Correlation of plasma levels of tumor necrosis factor, interleukin-6 and nitric oxide with the severity of human malaria. 1221 30

The anemia of chronic inflammatory and malignant diseases is partly due to impaired synthesis of the hormone erythropoietin (Epo). The proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha) suppress in vitro Epo gene expression and Epo protein secretion. However, the molecular mechanisms of this inhibition are poorly understood. The human Epo promoter and the 5' flanking region contain several recognition sequences for transcription factors acting either positively or negatively. Herein, we investigated the roles of the transcription factors GATA-2 and NF-kappaB in the modulation of Epo gene expression by IL-1beta and TNF-alpha in the human hepatoma cell line HepG2. Electrophoretic mobility shift assays revealed increased GATA-2 and NF-kappaB DNA binding in cells treated with IL-1beta or TNF-alpha. Reporter gene assays with a sequence from the Epo promoter in front of the firefly luciferase gene showed that the cytokines reduced Epo reporter gene activity. Functional inactivation of GATA-2 and NF-kappaB by oligo-decoy techniques prevented the inhibition of Epo production by IL-1beta and TNF-alpha. In HepG2 cells stably transfected with a dominant-negative form of IkappaBalpha, the activation of NF-kappaB was inhibited, while Epo mRNA levels and Epo secretion increased. Thus, both GATA-2 and NF-kappaB seem to be involved in the suppression of Epo gene expression by IL-1beta and TNF-alpha in vitro and may be responsible for impaired Epo synthesis in inflammatory diseases in vivo.
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PMID:Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA-2 and NF-kappaB. 1222 49

The intensity of malaria transmission is related to the pattern of malarial disease observed in different regions, but populations may also differ in their underlying predispositions to severe malarial anemia or cerebral malaria. In western Kenya, where severe malarial anemia is much more common than cerebral malaria, the distributions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, transforming growth factor (TGF)-beta, IL-6, and interferon (IFN)-gamma alleles were examined in a cohort of young men. The cohort displayed a marked bias toward genotypes associated with low expression of IFN-gamma and IL-6, cytokines that, at high levels, have been implicated in malarial anemia and poor malaria outcomes. By contrast, the frequency of the TNF-alpha -238A allele, which has been associated with severe malarial anemia, was found to be similar to the frequency previously reported in comparison populations in Africa and elsewhere. IFN-gamma and IL-6 genotypes may play roles in the development of severe malaria and could contribute to the relative frequency of severe malarial anemia or cerebral malaria in exposed populations.
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PMID:Profound bias in interferon-gamma and interleukin-6 allele frequencies in western Kenya, where severe malarial anemia is common in children. 1223 42

Experimental infection of non-human primates with simian malaria parasites offers a controlled system to study malarial immunity. Plasmodium cynomolgi (P. vivax-like) and P. knowlesi (P. falciparum-like) infections in the rhesus monkey were used as a model to test the hypothesis that initial acute infection stimulates type 1/pro-inflammatory cytokine expression followed by a gradual type 2/anti-inflammatory response upon re-infection. This study analyzed cytokine gene expression (interleukin-12, interferon-gamma, tumor necrosis factor-alpha = type 1; interleukin-4, interleukin-10 = type 2) using a semi-quantitative reverse transcriptase-polymerase chain reaction in monkeys infected with each of the parasites (three per group). Clinicoparasitologic and serologic parameters were also monitored. Monkeys were re-infected to assess whether enhanced immunity could increase parasite clearance. The immune response to P. cynomolgi infection in rhesus monkeys seemed to be mediated by anti-parasite, pro-inflammatory responses during primary infection with a transition to protective type 2 responses after repeat infection. The immune responses to P. knowlesi infection were more varied. Anti-inflammatory responses were more prevalent during primary infection. Repeat infection stimulated a wide variety of responses; most included expression of tumor necrosis factor-alpha, a cytokine that has been associated with inflammatory and host-destructive effects (weight loss, fever, anemia). These observations further confirmed that the simian malaria/rhesus monkey model is well suited for studies on the regulation of immunity to acute Plasmodium infection.
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PMID:Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium knowlesi infections. 1251 48

Here we describe a lethal mouse model infected with dengue virus type 2 with several similarities to human DEN-2 infection. Clinically animals demonstrated anemia, thrombocytopenia, pre-terminal paralysis and shock. The most impressive changes were seen with tumor necrosis factor (TNF)-alpha, which abruptly and steeply increased 24 h before the exitus (mean at day 6). Serum levels of IL-1beta, IL-6, IL-10, IL-1 receptor antagonist and soluble TNF receptor I continuously increased during the time of infection. A 100% mortality rate was noted in that group of animals. Treating animals with anti-TNF-alpha serum reduced mortality rate down to 40% (P<0.05). Our model supports the view that activation of innate immune response is at least partially responsible for mortality in DEN-2 infection, and in line with this concept, anti-TNF treatment significantly reduces mortality rates.
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PMID:Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection. 1258 55

More than 30% of cancer patients experience anemia and its side effect, fatigue. Its causes can be numerous, but anemia is usually secondary to an imbalance of cytokines. Among these, tumor necrosis factor-alpha seems to be the major culprit, creating anemia by blunting the physiological effect of erythropoietin. Pharmacologically increasing the erythropoietin level corrects the anemia in about half the treated patients. Several studies have shown that quality of life is substantially improved through such therapy.
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PMID:Anemia in cancer: some pathophysiological aspects. 1262 84

Hematopoietic progenitor cells from children with Fanconi anemia of the C complementation group (FA-C) are excessively apoptotic and hypersensitive to various extracellular cues including Fas-ligand, tumor necrosis factor-alpha and double-stranded RNA. Interferon (IFN)-gamma is known to augment apoptotic responses of these factors. The "priming" effect of IFN-gamma is not fully explained. In view of the strong evidence that FA cells are intolerant of oxidative stress, we tested the notion that IFN-priming involves the induction of reactive oxygen species (ROS) in two FA-C B-lymphocyte cell lines and in peripheral blood neutrophils and mononuclear cells of FA patients. We also investigated whether the combination of IFN-gamma and Fas created an intracellular environment that promoted apoptosis. Significantly lower doses of IFN-gamma induced ROS accumulation in neutrophils and mononuclear cell of FA patients compared to cells of normal individuals. Enhanced ROS accumulation and decreased intracellular glutathione levels were observed in FA-C B-cell lines primed with IFN-gamma and treated with agonistic anti-Fas antibody than in isogenic control cells corrected with FANCC. The above treatment also induced caspase-3 and -8 activation as well as apoptosis. That antioxidants reduced the priming effect of IFN-gamma in Fas and IFN-gamma-treated FA lymphoblast cells, demonstrates that ROS represent a critical effector mechanism for the exaggerated responses to IFN-gamma characteristic of FA-C cells.
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PMID:An oxidative mechanism of interferon induced priming of the Fas pathway in Fanconi anemia cells. 1262 94

Anemia of variable severity occurs in more than two-thirds of patients with multiple myeloma (MM). Besides the altered cytokine network, chronic erythropoietn deficiency, blood loss and hemolysis, we have shown that deregulated myeloma cell apoptosis contributes to progressive destruction of the erythroid matrix by inducing erythroblast cytotoxicity. To exert this effect, highly malignant plasma cells overexpress both Fas-L and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which efficiently trigger the death of immature erythroblasts. However, this Fas-L/TRAIL-based anemia occurs in particular in patients with severely progressive MM, thus suggesting that these apoptogen receptors may characterize a peculiar cytotoxic-apoptogenic phenotype of malignancy. Immunophenotyping of myeloma cells could help to identify patients with a higher risk of erythropoiesis exhaustion.
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PMID:Upregulation of erythroblast apoptosis by malignant plasma cells: a new pathogenetic mechanism of anemia in multiple myeloma. 1273 14


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