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)

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

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

Tumor necrosis factor alpha (TNF alpha) is usually excreted by the kidney. In dialysis patients, it accumulates. TNF alpha has been implicated in the pathogenesis of malnutrition, diabetic neuropathy, and erythropoietin resistance. We studied TNF alpha plasma levels in 49 stable peritoneal dialysis (PD) patients, with the aim of correlating those levels with the presence and severity of peripheral neuropathy, hypertrophic cardiomyopathy, and anemia. Kt/Vurea' residual renal creatinine clearance (CrC), nutritional markers, and general biochemistry were also determined. The average plasma level of TNF alpha was 67 +/- 32 pg/mL (range: 18.1-156.3 pg/mL; normal value 3-20 pg/mL). No correlation was observed between TNF alpha and KT/Vurea' but a negative correlation with CrC was seen (r: -0.37, p < 0.05). TNF alpha levels were higher in patients with neuropathy as compared to patients with normal results (72.5 +/- 32 pg/mL vs 44 +/- 22 pg/mL, p < 0.05). Patients with neuropathy also showed a lower CrC value (1.5 +/- 1.7 mL/min vs 3.9 +/- 2.6 mL/min, p < 0.01). TNF alpha levels were higher in patients with left ventricular hypertrophy (LVH) with respect to normal individuals (70.4 +/- 32 pg/mL vs 38.5 +/- 20.8 pg/mL, p < 0.05). Patients with severe LVH showed the lowest CrC value. A direct, significant relationship was found between TNF alpha levels and weekly erythropoietin dose (r: 0.41, p < 0.05). Patients with hypertriglyceridemia or taking lipid-lowering agents showed a positive linear correlation between TNF alpha and triglycerides (r = 0.7, n = 14, p < 0.05). These data suggest that accumulation of TNF alpha may contribute to the development or maintenance of some neurologic, hematologic, and cardiac complications of uremic syndrome. Loss of residual renal function conditions an increment in TNF alpha levels. These data continue to add support to the idea that TNF alpha may be considered a uremic toxin.
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PMID:Tumor necrosis factor alpha as a uremic toxin: correlation with neuropathy, left ventricular hypertrophy, anemia, and hypertriglyceridemia in peritoneal dialysis patients. 1068 77

The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than in the other clinical categories of P. falciparum malaria patients. Levels of both receptors depended on clinical category, whereas only sTNF-R1 levels were significantly dependent on parasitemia. Detailed analysis of the interrelationship between these variables resolved this pattern further, and identified marked differences between the patient categories. While levels of TNF, sTNF-R1 and sTNF-R2 correlated with parasitemia in UM, this was not the case in CM and SA. Rather, there was a tendency towards high levels of TNF and its receptors in CM and low levels in SA without significant correlation to parasitemia in either category. This, and the fact that malaria-induced increases in plasma levels of IL-10 are much lower in SA compared to CM, suggest that distinct forms of dysregulation of the immune response to infection contribute to the pathogenesis of CM and SA.
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PMID:Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria. 1070 8

Iron is essential for life. Inflammatory disorders cause iron metabolism disturbances resulting in very low concentration of free iron. Iron binding proteins synthesis have a central role in the decreasing iron reutilization for erythropoiesis, and in the increasing iron storage. Inflammatory disorders also induce inhibition of the erythroid progenitors. Synthesis and action of erythropoietin are also disturbed. All these changes are mediated by the activated cytokine cascade (TNF alpha, IL1, IL6...) that is able to induce anaemia of inflammation those clinical and biological characteristics are well defined. Soluble transferrin receptor concentration can help to identify iron deficiency when inflammation is associated. Management of anaemia of inflammation requires prior to treat the cause of inflammation when it is possible, even if human recombinant erythropoietin has been demonstrated to be effective.
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PMID:[Iron and inflammation]. 1086 94

Despite considerable progress in recent years in the understanding of the biology of multiple myeloma (MM), this disease remains incurable, although many new therapeutic approaches are under evaluation. The rapid development of recombinant technologies has permitted the production of large amounts of cytokines and growth factors, favoring the use of biotherapies also in this disease. Among these products, the interferons have been the most extensively used in clinical trials, giving the most promising results especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies, or to high dose chemotherapies followed by bone marrow (BM) or peripheral blood stem cell (PBSC) transplantation. However, more recently, a large number of cytokines and growth factors have been introduced in the clinical practice. Data of the use of erythropoietin have consistently demonstrated the role of this growth factor in ameliorating the grade of anemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Using hematopoietic growth factor in the mobilization of PBSC, the quantity of progenitor cells in the peripheral blood increased and the hematological toxicity of chemotherapy could be reduced. Despite the large amount of experimental data indicating a role for interleukins, as IL-2 and IL-6, in controlling tumor growth, there are only few clinical studies dealing with their use in MM. Results show that they arrest tumor progression rather than aid tumor regression, for this reason it appears that IL-2 and anti IL-6 antibodies should be investigated as maintenance therapy, in MM patients responding to chemotherapy. In the future it will be necessary to clarify for MM patients the role of other cytokines such as IL-1 beta and TNF alpha. A possible strategy to improve the clinical outcome of MM patients is to prevent the regrowth of residual tumor cells by establishing adoptive immunity at the stages of minimal residual disease previous obtained using chemotherapy. To this end a possible strategy is to induce an immune response against residual tumor cells by passive (using monoclonal antibodies) or active (using the idiotype expressed by malignant cells) immunotherapy.
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PMID:[The role of biotherapy in multiple myeloma]. 1107 35

Fatigue is prominent in cancer patients and probably multifactorial in origin. Factors contributing to fatigue include anemia, weight loss, fever, pain, medication, and infection. In cancer patients, many of these factors are influenced by a frequently disrupted balance between endogenous cytokine levels and their natural antagonists. Indeed, cancer cells and the immune system appear to overexpress a range of cytokines in patients with malignancies. Some of these cytokines act as autocrine or paracrine growth factors for the neoplastic tissue while simultaneously causing secondary symptoms related to fatigue. For instance, cancer-associated anemia may be due to a blunted erythropoietin response and/or cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-alpha [TNF-alpha]), which suppress erythropoiesis. Cancerous cachexia, a wasting syndrome and a hallmark of cancer, can be attributed to loss of appetite or enhanced energy expenditure. Several different interleukins, as well as TNF, interferon-gamma, and leukemia inhibitory factor, act as cachectins in animal models. Similarly, fever and night sweats are influenced by pyrogenic cytokines. Recently, molecules that function as cytokine antagonists have been identified. These molecules may be exploitable in combating the components of cancer-related fatigue, and may inhibit tumor growth as well.
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PMID:The role of cytokines in cancer-related fatigue. 1159 87

A polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene, with a guanine to adenine nucleotide change at position -308, TNF2 is associated with increased TNF-alpha production. TNF2 homozygotes have a higher risk of severe disease and/or death due to cerebral malaria and other infectious diseases. We investigated the impact of this allele on malaria morbidity and mortality in young children who participated in an immuno-epidemiologic cohort study of malaria in an area of intense perennial Plasmodium falciparum transmission in western Kenya. A total of 1,048 children were genotyped. Poisson regression and Cox proportional hazards models were used to determine the relationship between TNF-308 variants and morbidity and mortality. The gene frequencies of the TNF1 and TNF2 alleles were 0.90 and 0.10, respectively. TNF2 homozygosity was associated with pre-term birth when compared with TNF1 homozygotes [relative risk (RR) 7.3, 95% CI, 2.85-18.9, P = 0.002) and heterozygotes (RR 6.7, 95% CI 2.0-23.0, P = 0.008). Among children born prematurely, the TNF2 allele was significantly associated with a higher risk of death in infancy compared with TNF1 (RR 7.47, 95% CI 2.36-23.6). The risk of death was higher among TNF2 homozygotes than among heterozygotes. The TNF2 allele was significantly associated with high density P. falciparum parasitemia (RR 1.11, 95% CI 1.0-1.24). Among low birth weight children, the TNF2 allele was associated with severe anemia (RR 2.16, 95% CI 1.17-4.01) and showed a trend toward a risk for severe malaria anemia (RR 1.99, 95% CI 0.89-4.46). These data suggest that TNF2 is a risk factor for pre-term birth and early childhood mortality and malaria morbidity in children in this region. Further understanding of the pathogenic mechanisms underlying this association is required.
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PMID:Tumor necrosis factor-alpha promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX. 1166 77

Serum concentrations of antiinflammatory cytokines and growth factors were measured in 30 patients with chronic viral hepatitis (HCV), mainly HCV RNA, and 10 patients with liver cirrhosis (LC), classes B and C according to Child-Pew. Serum concentrations of tumor necrosis factor-alpha (TNF alpha), granulocytic-macrophagal colony-stimulating factor (GM-CSF), and growth-transforming factor-1 beta (TGF1 beta) were increased in 63.86 and 80% patients with HCV and LC, respectively, and differed significantly (p < 0.05) from the control. The level of TNF alpha positively correlated with the concentration of alanine aminotransferase (r = 0.14). A positive correlation between TGF1 beta and histologic activity index was detected (r = 0.16). Increased levels (p < 0.05) of IL-5, TNF alpha, and TGF1 beta were detected in LC patients in comparison with the control. Patients with LC concomitant with anemia had higher (though not significantly) concentrations of TNF alpha in comparison with patients without anemia. Increased levels of proinflammatory cytokines and growth factors in the sera of patients with HCV and LC indicate activation of immunocompetent cells, including mononuclear phagocytes. These data are in line with experimental findings, indicating an important role of the studied cytokines in the development of hepatic inflammation, fibrosis, and cytopenic syndromes.
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PMID:[Cytokine regulation of liver inflammation and fibrosis during chronic hepatic diseases]. 1184 Aug 29

Trypanosome infections are marked by severe pathological features, including anemia, splenomegaly, and suppression of T-cell proliferation. We have used lymphotoxin-alpha-deficient (LT-alpha(-/-)) mice, as well as LT-alpha-tumor necrosis factor-double-deficient (LT-alpha(-/-) TNF(-/-)) mice, to analyze the contributions of these related cytokines in both induction of trypanosomosis-associated immunopathology and infection control. Moreover, as the cytokine-deficient mice used have no detectable lymph nodes and lack germinal-center formation upon immune stimulation, we have analyzed the functional importance of both the lymph nodes and spleen during experimental Trypanosoma brucei infections. First, we show that the absence of LT-alpha does not significantly alter early trypanosomosis development or pathology but does result in better control of late-stage parasitemia levels and slightly prolonged survival. This increased survival of infected LT-alpha(-/-) mice coincides with the appearance of increased chronic-stage anti-trypanosome immunoglobulin M (IgM)-IgG2a serum titers that are generated in the absence of functional peripheral lymphoid tissue and do not require germinal-center formation. Second, we show that splenectomized mice control their parasitemia to the same extent as fully immune-competent littermates. Finally, using LT-alpha(-/-) TNF(-/-) double-deficient mice, we show that in these mice T. brucei infections are very well controlled during the chronic infection stage and that infection-induced pathology is minimized. Together, these findings indicate that while increased IgM-IgG2a anti-trypanosome antibody titers (generated in the absence of LT-alpha, peripheral lymph nodes, and germinal-center formation) coincide with improved parasitemia control, it is TNF that has a major impact on trypanosomosis-associated immunopathology.
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PMID:Control of experimental Trypanosoma brucei infections occurs independently of lymphotoxin-alpha induction. 1185 19


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