scholarly journals Tumor Necrosis Factor Receptor 1 Expression Is Upregulated in Dendritic Cells in Patients with Chronic HCV Who Respond to Therapy

2010 ◽  
Vol 2010 ◽  
pp. 1-10
Author(s):  
Raul Cubillas ◽  
Katherine Kintner ◽  
Frances Phillips ◽  
Nitin J. Karandikar ◽  
Dwain L. Thiele ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Mrna Levels ◽  
Specific Subset ◽  
Significant Difference ◽  
Chronic Hcv ◽  
Necrosis Factor

The present studies assessed the level of tumor necrosis factor receptor (TNFR) expression in peripheral blood mononuclear cells (PBMCs) subsets from patients with chronic HCV undergoing interferon /ribavirin-based therapy (Ifn/R). Methods. TNFR family member mRNA expression was determined using quantitative real-time PCR assays (RTPCRs) in PBMC from 39 HCV+ patients and 21 control HCV patients. Further subset analysis of HCV + patients (untreated (U), sustained virological responders (SVR), and nonresponders (NR)/relapsers (Rel)) PBMC was performed via staining with anti-CD123, anti-CD33, anti-TNFR1 or via RTPCR for TNFR1 mRNA. Results. A similar level of TNFR1 mRNA in PBMC from untreated HCV+ genotype 1 patients and controls was noted. TNFR1 and TNFR2 mRNA levels in PBMC from HCV+ patients with SVR were statistically different than levels in HCV() patients. A significant difference was noted between the peak values of TNFR1 of the CD123+ PBMC isolated from SVR and the NR/Rel. Conclusion. Upregulation of TNFR1 expression, occurring in a specific subset of CD123+ dendritic cells, appeared in HCV+ patients with SVR.

scholarly journals Fatal Granuloma Necrosis without Exacerbated Mycobacterial Growth in Tumor Necrosis Factor Receptor p55 Gene-Deficient Mice Intravenously Infected with Mycobacterium avium

1999 ◽  
Vol 67 (7) ◽  
pp. 3571-3579 ◽  
Author(s):  
Stefan Ehlers ◽  
Jochen Benini ◽  
Stefanie Kutsch ◽  
Robert Endres ◽  
Ernst T. Rietschel ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Mycobacterium Avium ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Mycobacterial Infection ◽  
Interleukin 12 ◽  
Mrna Levels ◽  
Reverse Transcription Pcr ◽  
Granulomatous Lesions ◽  
Necrosis Factor

ABSTRACT The pathogenesis of mycobacterial infections is associated with the formation of granulomas in which both antibacterial protection and tissue damage take place concomitantly. We used murineMycobacterium avium infection to compare the development of granulomatous lesions in intravenously infected tumor necrosis factor receptor p55 (TNFRp55) gene-deficient (p55−/−) mice to the development of granulomatous lesions in M. avium-infected syngeneic C57BL/6 (p55+/+) mice. Up to 5 weeks after infection with either the highly virulent M. avium strain TMC724 or the intermediately virulent M. avium strain SE01, bacterial counts in the liver, spleen, and lung of p55−/− mice were identical to or lower than those in infected p55+/+ mice. However, the formation of mononuclear cell foci in the liver was delayed by approximately 2 to 3 weeks in p55−/− mice compared to the results obtained for infected p55+/+ mice. Despite comparable bacterial loads, granulomas in p55−/− mice underwent progressive necrosis, causing damage to the surrounding liver tissue. The appearance of necrotizing granulomas was associated with the death of all infected p55−/− mice, regardless of the virulence of the M. avium strain used for infection. Granulomatous lesions in the liver contained three times as many CD3+ cells in p55−/− mice yet appeared more diffuse than in p55+/+ mice. Semiquantitative reverse transcription-PCR studies revealed that prior to mouse death, interleukin-12 (IL-12) and gamma interferon mRNA levels were up regulated in the livers of infected p55−/− mice, while mRNA levels for tumor necrosis factor, the inducible isoform of nitric-oxide synthase (iNOS), and IL-10 were similar to those found in infected p55+/+mice. In response to persistent mycobacterial infection, the absence of TNFRp55 causes the disregulation of T-cell–macrophage interactions and results in fatal granuloma necrosis even when adequate antibacterial functions are maintained.

scholarly journals Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 113-118 ◽  
Author(s):  
H Tilg ◽  
E Trehu ◽  
MB Atkins ◽  
CA Dinarello ◽  
JW Mier
Keyword(s):  
Detection Limit ◽  
Tumor Necrosis Factor ◽  
Receptor Antagonist ◽  
Plasma Levels ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Peripheral Blood Mononuclear ◽  
Soluble Tnf Receptor ◽  
Necrosis Factor

The aim of this study was to investigate whether interleukin (IL)-6 induces the production of IL-1 and tumor necrosis factor (TNF) antagonists. Serial plasma samples were obtained from cancer patients participating in phase I and II trials of recombinant IL-6 administered as a 120-hour continuous intravenous (IV) infusion. Plasma IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor p55 (TNFsRp55) levels were measured by specific radioimmunoassays (RIAs). IL-1Ra levels increased rapidly, reaching peak values (9.6 +/- 1.7 ng/mL) within 2 to 4 hours of beginning treatment. Thereafter, levels promptly declined, reaching near baseline within 24 hours despite continuation of IL-6. TNFsRp55 plasma levels increased within 4 to 8 hours after initiating treatment and increased progressively throughout the duration of therapy. IL-1 beta and TNF-alpha plasma levels were below the detection limit in all samples tested. Peripheral blood mononuclear cells (PBMC) exposed to IL-6 produced only small amounts (1.56 +/- 0.3 ng/mL) of IL-1Ra, even in the presence of exogenous soluble IL-6 receptor (gp80). TNFsRp55 levels measured in the supernatants of IL-6- stimulated PBMC were below the detection limit of the assay. Macrophages generated by culturing monocytes in granulocyte-macrophage colony-stimulating factor (GM-CSF) were much more responsive to IL-6 than freshly isolated unfractionated or adherent PBMC and synthesized almost as much IL-1Ra when stimulated with IL-6 as with endotoxin. These results suggest that the antinflammatory properties of IL-6 may be due; in part, to the induction of IL-1Ra synthesis and the release of soluble TNF receptors. Our findings also suggest that tissue macrophages may be an important source of IL-6-induced IL-1Ra.

scholarly journals Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 113-118 ◽  
Author(s):  
H Tilg ◽  
E Trehu ◽  
MB Atkins ◽  
CA Dinarello ◽  
JW Mier
Keyword(s):  
Detection Limit ◽  
Tumor Necrosis Factor ◽  
Receptor Antagonist ◽  
Plasma Levels ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Peripheral Blood Mononuclear ◽  
Soluble Tnf Receptor ◽  
Necrosis Factor

Abstract The aim of this study was to investigate whether interleukin (IL)-6 induces the production of IL-1 and tumor necrosis factor (TNF) antagonists. Serial plasma samples were obtained from cancer patients participating in phase I and II trials of recombinant IL-6 administered as a 120-hour continuous intravenous (IV) infusion. Plasma IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor p55 (TNFsRp55) levels were measured by specific radioimmunoassays (RIAs). IL-1Ra levels increased rapidly, reaching peak values (9.6 +/- 1.7 ng/mL) within 2 to 4 hours of beginning treatment. Thereafter, levels promptly declined, reaching near baseline within 24 hours despite continuation of IL-6. TNFsRp55 plasma levels increased within 4 to 8 hours after initiating treatment and increased progressively throughout the duration of therapy. IL-1 beta and TNF-alpha plasma levels were below the detection limit in all samples tested. Peripheral blood mononuclear cells (PBMC) exposed to IL-6 produced only small amounts (1.56 +/- 0.3 ng/mL) of IL-1Ra, even in the presence of exogenous soluble IL-6 receptor (gp80). TNFsRp55 levels measured in the supernatants of IL-6- stimulated PBMC were below the detection limit of the assay. Macrophages generated by culturing monocytes in granulocyte-macrophage colony-stimulating factor (GM-CSF) were much more responsive to IL-6 than freshly isolated unfractionated or adherent PBMC and synthesized almost as much IL-1Ra when stimulated with IL-6 as with endotoxin. These results suggest that the antinflammatory properties of IL-6 may be due; in part, to the induction of IL-1Ra synthesis and the release of soluble TNF receptors. Our findings also suggest that tissue macrophages may be an important source of IL-6-induced IL-1Ra.

scholarly journals Interferon-alpha induces circulating tumor necrosis factor receptor p55 in humans

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 433-435
Author(s):  
H Tilg ◽  
W Vogel ◽  
CA Dinarello
Keyword(s):  
Tumor Necrosis Factor ◽  
Interferon Alpha ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Tumor Necrosis Factor Receptor ◽  
Tnf Alpha ◽  
Peripheral Blood Mononuclear ◽  
Ifn Alpha ◽  
Necrosis Factor

In the present studies we investigated the effect of interferon-alpha (IFN alpha) on the release of the soluble (extracellular) form of the tumor necrosis factor p55 receptor (TNFsRp55), because TNFsRp55 is a natural antagonist of tumor necrosis factor (TNF)-induced inflammation and also might be part of the antiinflammatory properties of IFN alpha. Plasma levels of TNFsRp55 were measured by a specific radioimmunoassay in five healthy volunteers and in five patients with chronic hepatitis C treated with IFN alpha. Levels showed a significant increase after a single injection of 5.0 million U IFN alpha in both healthy and hepatitis patient groups. Peak values (3.5 to 4.5 ng/mL) were observed within 12 hours of beginning treatment. Thereafter, levels promptly declined, reaching baseline values within 24 hours. TNF alpha and C- reactive protein (CRP) levels were below the detection limit in the same plasma samples. In addition, IFN alpha suppressed significantly interleukin (IL)-1 alpha-induced TNF alpha protein synthesis by human peripheral blood mononuclear cells. These results suggest that the antiinflammatory properties of IFN alpha may be, in part, also due to the induction and/or release of TNF soluble receptors and the suppression of TNF alpha synthesis.

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