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T lymphocyte activation and increased cytokine levels have been described in retrospective studies of children presenting with dengue hemorrhagic fever (DHF). Serial plasma samples obtained in a prospective study of Thai children ...
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T lymphocyte activation and increased cytokine levels have been described in retrospective studies of children presenting with dengue hemorrhagic fever (DHF). Serial plasma samples obtained in a prospective study of Thai children presenting with <72 h of fever were studied. Plasma levels of 80-kDa soluble tumor necrosis factor receptors (sTNFRs) were higher in children who developed DHF than in those with dengue fever (DF) or other nondengue febrile illnesses (OFIs) and were correlated with the degree of subsequent plasma leakage. Soluble CD8 and soluble interleukin-2 receptor levels were also elevated in children with DHF compared with those with DF. Interferon-gamma and sTNFR 60-kDa levels were higher in children with dengue than in those with OFIs. TNF-alpha was detectable more often in DHF than in DF or OFIs (P<.05). These results support the hypothesis that immune activation contributes to the pathogenesis of DHF. Further studies evaluating the predictive value of sTNFR80 for DHF are warranted.
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This study investigated the plasma levels of tumor necrosis factor a (INF-alpha) and the expression levels of TNF receptors (TNFRs) in patients with multiple trauma, together with the association between the levels of this cytokin...
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This study investigated the plasma levels of tumor necrosis factor a (INF-alpha) and the expression levels of TNF receptors (TNFRs) in patients with multiple trauma, together with the association between the levels of this cytokine and these cytokine receptors with the severity of traumatic injury. Blood samples were obtained from 60 multiple trauma patients at hospital admission (within 2 h of injury), and 6-8 h and 1-5 days after admission. The plasma levels of TNF-alpha and TNFR1/TNFR2 were detected using enzyme immunoassay. TNFR1 and TNFR2 expression levels on leukocytes, including neutrophils, lymphocytes and monocytes, were determined by flow cytometry. Clinical parameters were determined by injury severity score (ISS). At hospital admission, the plasma TNF-alpha and soluble TNFR levels in the trauma patients were elevated compared with those of healthy controls. Increased expression levels of TNFR1 and TNFR2 were also detected on leukocytes, particularly on lymphocytes and monocytes. The expression levels of the cytokine and the corresponding receptors were correlated with the ISS. TNF-alpha and TNFR expression levels remained significantly elevated for up to the third to fifth day following the traumatic injury. In the trauma patients, increased levels of TNF-alpha and TNFRs were correlated with the severity of traumatic injury in the early post-injury period, supporting the hypothesis that trauma-provoked organ dysfunction may be caused by an overwhelming auto-destructive inflammatory response.
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Genetic iron overload, or hemochromatosis, can be caused by mutations in HFE, hemojuvelin, and hepcidin genes. Hepcidin, a negative regulator of intestinal iron absorption, is found to be inappropriately low in both patients and i...
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Genetic iron overload, or hemochromatosis, can be caused by mutations in HFE, hemojuvelin, and hepcidin genes. Hepcidin, a negative regulator of intestinal iron absorption, is found to be inappropriately low in both patients and in animal models, indicating that proper control of basal hepcidin levels requires both hemojuvelin and HFE. In mice, repulsive guidance molecule c (Rgmc, the hemojuvelin mouse ortholog) and hepcidin levels are transcriptionally regulated during inflammation. Here, we report that basal Rgmc levels in Hfe-deficient mice are normal and that these mice retain the ability to suppress Rgmc expression after lipopolysaccharide (LPS) challenge. Thus, Rgmc regulation by LPS is Hfe-independent. The response of Rgmc to LPS involves signaling through toll-like receptor 4 (Tlr4), because Tlr4-deficient mice do not show altered Rgmc expression after LPS administration. We further show that tumor necrosis factor-, but not interleukin-6, is sufficient to cause Rgmc down-regulation by LPS. These results contrast with previous data demonstrating that hepcidin levels are directly regulated by interleukin-6 but not by tumor necrosis factor-. The regulation of iron-related genes by different cytokines may allow for time-dependent control of iron metabolism changes during inflammation and may be relevant to chronic inflammation, infections, and cancer settings, leading to the development of anemia of chronic disease.
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Objectives: Few genetic markers for the prognosis of sarcoidosis have been found. Tumor
necrosis factor (TNF)-a has been implicated in the pathogenesis of sarcoidosis. Induced TNF-a
or TNF-b levels have been shown to be associated...
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Objectives: Few genetic markers for the prognosis of sarcoidosis have been found. Tumor
necrosis factor (TNF)-a has been implicated in the pathogenesis of sarcoidosis. Induced TNF-a
or TNF-b levels have been shown to be associated with the polymorphisms of the TNF genes. We
investigated the roles of such polymorphisms in the development and prolongation of sarcoidosis.
Subjects and measurements: One hundred ten Japanese patients with sarcoidosis and 161 con-
trol subjects were genotyped for three biallelic polymorphisms in the promoter region of TNF-a
gene by direct sequencing of polymerase chain reaction (PCR) products. A polymorphism of the
TNF-b gene (TNFB*
1/TNFB*
2) was detected by Nco I restriction fragment length polymorphism
analysis of PCR products spanning intron 1 and exon 2 of the TNF-b gene.
Results: None of the polymorphisms conferred susceptibility to sarcoidosis. However, our study
identified the allele TNFB*
1, detected by the presence of a Nco I restriction site, as a marker of
prolonged clinical course, with the resolution of sarcoidosis being defined as the disappearance
of all clinical symptoms, physical signs of active lesions, abnormal chest radiograph findings, and
abnormal results of pulmonary function and biochemical tests. When the probability of remission
in patients homozygous for TNFB*
2 was defined as 1.00, it was 0.48 (95% confidence interval,
0.26 to 0.88; p < 0.05) in patients with TNFB*
1 (genotypes TNFB*
1/1 and TNFB*
1/2).
Conclusions: The TNFB*
1 allele is a marker for prolonged clinical course in patients with
sarcoidosis. Our study is the first to link a cytokine gene polymorphism to the prognosis of
sarcoidosis.
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The major evolutionary advance represented in the human immune system is a mechanism of antigen-directed immunity in which tumor necrosis factor (TNF)-α and TNF receptors (TNFRs) play essential roles. Binding of TNF-α to the 55-...
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The major evolutionary advance represented in the human immune system is a mechanism of antigen-directed immunity in which tumor necrosis factor (TNF)-α and TNF receptors (TNFRs) play essential roles. Binding of TNF-α to the 55-kDa type I TNFR (TNFR1, TNFRSF1A, CD120a, p55) or the 75-kDa type II TNFR (TNFR2, TNFRSF1B, CD120b, p75) activates signaling pathways controlling inflammatory, immune and stress responses, as well as host defense and apoptosis. Multiple studies have investigated the role of TNFRs in the development of early and late renal failure (diabetic nephropathy, nephroangiosclerosis, acute kidney transplant rejection, renal cell carcinoma, glomerulonephritis, sepsis and obstructive renal injury). This article reviews the general characteristics, the analytical aspects and the biology of TNFRs in this domain. In addition, the potential therapeutic application of specific TNFR blockers is discussed.
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Background: Previous research has shown that infliximab (IFX) is effective in the management of moderate to severe active ulcerative colitis (UC). Latin American studies are lacking. Aim: To evaluate the efficacy of IFX treatment ...
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Background: Previous research has shown that infliximab (IFX) is effective in the management of moderate to severe active ulcerative colitis (UC). Latin American studies are lacking. Aim: To evaluate the efficacy of IFX treatment (including corticosteroid withdrawal, complete mucosal healing, colectomy and hospitalization rates) in patients with moderate to severe UC. Methods: A retrospective and descriptive study was conducted on patients with UC in Medellín (Colombia). We included patients steroid dependent or refractory to conventional treatment. Results: Between October 2005 and July 2011, 28 patients with moderate to severe UC received IFX infusions; the median of the follow-up was 27.4 months (range: 1-69 months). Twenty-four patients (86%) had a short-term primary response, whilst 19 (68%) achieved initial clinical remission. After 1 year, 17 (71%) out of the 24 patients who had an initial response were also showing a sustained response, and 10 (42%) remained in clinical remission. At 6 months, complete mucosal healing was observed in 29% of patients and endoscopic improvement in 57%. Conclusions: This is the first study to evaluate the IFX use in patients with moderate to severe active UC in a Latin American population. We found that IFX therapy is effective for inducing clinical remission, and that most patients who had an initial response showed a long-term sustained response.
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Purpose The formation of retinal neovascularization (RNV) is the primary pathological process underlying retinopathy of prematurity (ROP). Previous studies have shown that inflammatory factors are related to the formation of RNV. ...
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Purpose The formation of retinal neovascularization (RNV) is the primary pathological process underlying retinopathy of prematurity (ROP). Previous studies have shown that inflammatory factors are related to the formation of RNV. Tumor necrosis factor-alpha (TNF-alpha), as an important factor in the inflammatory response, is involved in the regulation of RNV formation. However, the mechanism through which TNF-alpha inhibition reduces RNV formation is not fully clarified. Therefore, the purpose of this study was to explore the effect of etanercept, an inhibitor of TNF-alpha, on RNV, and its possible mechanism.
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Tumor necrosis factor-α (TNFα) is a main actor in the pathogenesis of rheumatoid arthritis (RA), interacting with other molecules in complex mechanisms. The neuroendocrine system is known to be involved and Chromogranin A (CHGA)...
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Tumor necrosis factor-α (TNFα) is a main actor in the pathogenesis of rheumatoid arthritis (RA), interacting with other molecules in complex mechanisms. The neuroendocrine system is known to be involved and Chromogranin A (CHGA) serum levels are elevated in patients with RA. We evaluated the effect of the selective blockade of TNF-α, induced by treatment with anti-TNF-α monoclonal antibodies (mAbs), on the serum levels of CHGA and on its correlation with TNF-α and TNF-α receptors (TNFRs) serum levels. Seven patients with RA have been treated with the anti-TNF-α mAb, infliximab. We measured the serum levels of TNF-α, its receptors (tumor necrosis factor receptor-Ⅰ [TNFR-Ⅰ] and tumor necrosis factor receptor-Ⅱ [TNFR-Ⅱ]), and CHGA before and during the treatment. We also measured, as a control, the serum levels of CHGA, TNF-α, and soluble TNFRs in 14 patients who were being treated with infliximab, adalimumab, or etan-ercept and in 20 matching negative controls. The serum levels of TNFR-Ⅰ and TNFR-Ⅱ, which are a sensitive marker for the TNF-α pathway, correlated with those of CHGA before treatment (Pearson's coefficient, respectively, 0.59 and 0.53). Treatment with anti-TNF-α mAb provided a significant clinical response in all patients and the correlation between CHGA and TNFR-Ⅰ and TNFR-Ⅱ was no more evident during treatment (respectively, -0.09 and -0.07). TNF-α blockade allows a clinical effect in patients with RA and modifies the correlation between CHGA and TNFRs, suggesting that TNF-α and CHGA reciprocally interfere in the pathogenesis of RA, through intermediate adaptors, whose identification warrants further studies.
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Vascular endothelial growth factor C (VEGF-C) plays an important role in the development of a pterygium through lymphangiogenesis. We examined the association between VEGF-C and tumor necrosis factor- (TNF-) in the pathogenesis of...
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Vascular endothelial growth factor C (VEGF-C) plays an important role in the development of a pterygium through lymphangiogenesis. We examined the association between VEGF-C and tumor necrosis factor- (TNF-) in the pathogenesis of pterygia. Cultured conjunctival epithelial cells were treated with TNF-, and the gene expression levels of VEGFC were evaluated by quantitative polymerase chain reaction (qPCR) and VEGF-C protein expression levels were measured using an enzyme-linked immunosorbent assay (ELISA). In addition, using ELISA, we evaluated the VEGF-C protein expression in the supernatants of cultured conjunctival epithelial cells, in which we neutralized TNF- using anti-TNF- antibody. The gene expression of tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), known as TNF receptor 1 (TNFR1), was confirmed using reverse transcription PCR in cultured conjunctival epithelial cells. Immunofluorescence microscopy was used to examine the localization of VEGF-C and TNFR1 in pterygium tissues and TNFR1 expression in cultured conjunctival epithelial cells. Immunohistochemistry was used to examine the localization of TNFR1 in pterygia and normal conjunctival tissues. VEGFC gene expression increased in cultured conjunctival epithelial cells 24 h after the addition of TNF-. The secretion of VEGF-C protein was significantly increased 48 h after the stimulation of cultured conjunctival epithelial cells with TNF-. Increased VEGF-C protein secretion stimulated by TNF- was significantly reduced by anti-TNF- neutralizing antibody treatment. In cultured conjunctival epithelial cells, TNFRSF1A and TNFR1 were expressed. TNFR1 was immunolocalized in normal conjunctival tissues and in human pterygium tissues as well as in VEGF-C-positive epithelial cells from human pterygia. Our data demonstrate that TNF- mediates VEGF-C expression, which plays a critical role in the pathogenesis of pterygia.
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