Evaluation of angiogenis activation during interleukin-2 infusion in patients with renal cell cancer (RCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14640-14640
Author(s):  
C. Simonelli ◽  
R. Talamini ◽  
A. Bearz ◽  
M. Berretta ◽  
P. Monini ◽  
...  
Keyword(s):  
Cell Cancer ◽  
Interleukin 2 ◽  
Angiogenesis Inhibitors ◽  
Angiogenic Factor ◽  
Inflammatory Factors ◽  
Cytokine Network ◽  
Tnf Α ◽  
Ifn Γ ◽  
Few Data ◽  
Factor Release

14640 It is well known that during IL-2 administration a complex activation of the cytokine network is on going, but few data are available about the effect of this activation on angiogenesis. In our Institution all patients with metastatic RCC undergo to the following schedule of IL-2 infusion: IL-2 10 MIU continuous infusion (ci) 5/7 days, one week off followed by IL-2 10 MIU ci 5/7 days, 4 week off (1 cycle); for a total number of 2 cycles. We evaluated the activation of angiogenesis measuring the plasma level of VEGF MMP2 and MMP9 before, during and after the 5 days IL-2 ci. In 13 patients analysed, before IL-2 ci, we have the following median level of plasma VEGF (773+ 378 pg/ml), MMP2 (55.9 + 19.9 ng/ml) and MMP9 (1146+498 ng/ml). The baseline median values of VEGF MMP-9 showed a trend to correlate with the number of metastasis before therapy. During 3 days of IL-2 ci we did not observed any significant increase of VEGF MMP2 and MMP9 as well as after 24 hours from the end of the 5 days ci. On the contrary, at the same time-points, during and after IL-2 ci, we observed the activation of pro-inflammatory cytokines network, measured by the statistically significant increased levels of neopterin IFN-γ and TNF-α and sIcam.This preliminary observation demonstrated that IL-2 ci, even if it highly activates the release of pro-inflammatory factors, does not affect the release of angiogenic surrogate markers such as VEGF MMP2 and MMP9. On the basis of our experience we can suggest that the most suitable time to test angiogenesis inhibitors during IL-2 therapy appear to be the intervals between IL-2 administration and not during IL-2 infusion when the most severe side effects occur and it is not observed a significant increase of angiogenic factor release. No significant financial relationships to disclose.

scholarly journals Detection of soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 in the effusion of otitis media with effusion

1995 ◽  
Vol 4 (5) ◽  
pp. 350-354 ◽  
Author(s):  
T. Ganbo ◽  
K.-I. Hisamatsu ◽  
H. Inoue ◽  
K. Kikushima ◽  
A. Mizukoshi ◽  
...  
Keyword(s):  
Otitis Media ◽  
Otitis Media With Effusion ◽  
Interleukin 2 ◽  
Intercellular Adhesion Molecule ◽  
Healthy Controls ◽  
Intercellular Adhesion Molecule 1 ◽  
Cytokine Network ◽  
Tnf Α ◽  
Soluble Interleukin 2 Receptor ◽  
Soluble Intercellular Adhesion Molecule

We measured sIL-2R, TNF-α and sICAM-1 in the sera and middle ear effusions (MEEs) of patients with otitis media with effusion (OME). Although there was no signmcant difference between the sIL-2R levels of the serous and mucoid MEEs, they were significantly higher than serum sIL-2R levels of OME patients and healthy controls. TNF-α levels of the mucoid MEEs were significantly higher than those of the serous type. However, TNF-α was rarely detected in the sera of OME patients or healthy controls. We observed significant differences between the serous and mucoid MEEs with respect to their sICAM-1 levels, which were also higher than serum slCAM-1 levels of OME patients and healthy controls. Our findings suggested that IL-2, TNF-α and ICAM-1 could be significantly involved in the pathogenesis of OME through the cytokine network.

Intracellular Cytokine Profile of Cord and Adult Blood Lymphocytes

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 11-18 ◽  
Author(s):  
I.M.H. Chalmers ◽  
G. Janossy ◽  
M. Contreras ◽  
C. Navarrete
Keyword(s):  
Flow Cytometry ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Cytokine Profile ◽  
Color Flow ◽  
Blood Lymphocytes ◽  
Tnf Α ◽  
Ifn Γ

Umbilical cord blood (CB) transplantation is thought to be associated with a reduced risk of severe graft-versus-host-disease (GVHD) compared with bone marrow transplantation (BMT). The cytokine cascade is known to be important in the pathogenesis of GVHD; however, previous studies investigating the cytokine secretion pattern of CB cells have been contradictory because of variations in experimental techniques. In this study, the cytokine profile of cord and adult blood lymphocytes and lymphocyte subsets has been assessed at the single-cell level by flow cytometry, using CD4/CD8 and CD45RA/CD45RO markers. Cord and adult blood mononuclear cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin in the presence of monensin. After 4 to 24 hours of incubation, interleukin-2 (IL-2), IL-4, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) production was measured by three-color flow cytometry. The results show that cord blood lymphocytes (CBL) produce less IL-2, IL-4, IFN-γ, and TNF-α than adult peripheral blood lymphocytes (ABL). Further subset analysis showed that in CBL the majority of cytokine producing cells were CD4+CD45RA+, whereas in ABL the cytokine-producing cells were both CD4+CD45RO+ and CD8+CD45RO+. These results suggest that the reduced incidence of GVHD in CB transplantation may partly due to the altered cytokine profile seen in CBL.

Targeting bioenergetics prevents CD4 T cell–mediated activation of synovial fibroblasts in rheumatoid arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2816-2828 ◽  
Author(s):  
Andreea Petrasca ◽  
James J Phelan ◽  
Sharon Ansboro ◽  
Douglas J Veale ◽  
Ursula Fearon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adhesion Molecule ◽  
Cd4 T Cells ◽  
Reciprocal Relationship ◽  
Angiogenic Factor ◽  
Flux Analysis ◽  
Intracellular Cytokines ◽  
Tnf Α ◽  
Ifn Γ

Abstract Objectives We investigated the reciprocal relationship linking fibroblast-like synoviocytes (FLS) and T lymphocytes in the inflamed RA synovium and subsequently targeted cellular metabolic pathways in FLS to identify key molecular players in joint inflammation. Methods RA FLS were cultured with CD4 T cells or T cell conditioned medium (CD4CM); proliferation, expression of adhesion molecules and intracellular cytokines were examined by flow cytometry. FLS invasiveness and secreted cytokines were measured by transwell matrigel invasion chambers and ELISA, while metabolic profiles were determined by extracellular Seahorse flux analysis. Gene expression was quantified by real-time quantitative RT-PCR. Results Our results showed mutual activation between CD4 T cells and FLS, which resulted in increased proliferation and expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 by both CD4 T cells and FLS. Furthermore, interaction between CD4 T cells and FLS resulted in an increased frequency of TNF-α+, IFN-γ+ and IL-17A+ CD4 T cells and augmented TNF-α, IFN-γ, IL-17A, IL-6, IL-8 and VEGF secretion. Moreover, CD4CM promoted invasiveness and boosted glycolysis in FLS while downregulating oxidative phosphorylation, effects paralleled by increased glucose transporters GLUT1 and GLUT3; key glycolytic enzymes GSK3A, HK2, LDHA and PFKFB3; angiogenic factor VEGF and MMP-3 and MMP-9. Importantly, these effects were reversed by the glycolytic inhibitor 2-DG and AMP analogue 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Conclusion This study demonstrates that CD4 T cells elicit an aggressive phenotype in FLS, which subsequently upregulate glycolysis to meet the increased metabolic demand. Accordingly, 2-DG and AICAR prevent this activation, suggesting that glycolytic manipulation could have clinical implications for RA treatment.

scholarly journals Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys

2008 ◽  
Vol 82 (10) ◽  
pp. 4844-4852 ◽  
Author(s):  
Jinyan Liu ◽  
Bonnie A. Ewald ◽  
Diana M. Lynch ◽  
Matthew Denholtz ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Rhesus Monkeys ◽  
Recombinant Adenovirus ◽  
Interleukin 2 ◽  
Cellular Immune Responses ◽  
Tnf Α ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Lymphocyte Responses

ABSTRACT Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-γ+) and IFN-γ+/tumor necrosis factor alpha+ (TNF-α+) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2+ (IL-2+) and polyfunctional IFN-γ+/TNF-α+/IL-2+ T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.

scholarly journals Hepatic Lipidomics Reveals the Homeostasis and Profile of Sphingomyelin from Yak Butter in Normal-Fat Diet-Fed Rats

2020 ◽  
Author(s):  
Xin LUO ◽  
Wancheng SUN ◽  
Yihao LUO
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Metabolic Pathways ◽  
High Fat Diet ◽  
Liver Lipid ◽  
Normal Diet ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Liver Lipid Metabolism ◽  
Ifn Γ

Abstract Background: Dietary sphingomyelin was showed to inhibit the uptake of lipids in mice fed with a high-fat diet, however, the effect of sphingomyelin on normal diet was on reported. The current study aims to examine the effects of sphingomyelin extracts from yak butter on hepatic steatosis and inflammation in C57/B6J mice fed with a normal diet. Methods: A UHPLC-QTOF-MS based lipidomics method was utilized to screen the liver metabolites and predict the dominant potential metabolic pathways after sphingomyelin feeding. Results: The results showed that sphingomyelin extracts reduced the accumulation of lipid droplets, suppressed the expression of pro-inflammatory factors IFN -γ, IL-6 and TNF - α, synchronously, promoted the expression of anti-inflammatory factors IL-10, IL-4 and IL-1Ra. In addition, sphingomyelin extracts exhibited the modulation on liver lipid metabolism when supplement sphingomyelin in normal diet for one month and five months. Specifically, 16, 68 different metabolites and 2, 6 metabolic pathways were identified by quantitative lipidomics, respectively. Six CERs including Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d17:1/22:0), Cer(d17:1/24:1), Cer(d17:1/24:0) and Cer(d17:0/26:1), six SMs including SM(d15:0/24:1), SM(d14:0/26:1), SM(d14:1/24:1), SM(d15:1/22:0), SM(d15:1/24:1) and SM(d19:1/26:1), and PS(18:1/22:6) were identified and can be used as potential biomarkers of steatosis and inflammation.Conclusions: This study highlighted the effects of yak butter sphingomyelin on hepatic steatosis, tissue inflammation and lipid metabolism of mice under a normal diet.

scholarly journals Differential Regulation of Cytokine Production by CD1d-Restricted NKT Cells in Response to Superantigen Staphylococcal Enterotoxin B Exposure

2006 ◽  
Vol 74 (1) ◽  
pp. 282-288 ◽  
Author(s):  
Melanie J. Ragin ◽  
Nisebita Sahu ◽  
Avery August
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Nkt Cells ◽  
Staphylococcal Enterotoxin ◽  
Cytokine Secretion ◽  
Staphylococcal Enterotoxin B ◽  
Tnf Α ◽  
Ifn Γ ◽  
Enterotoxin B

ABSTRACT NKT cells are a heterogeneous population characterized by the ability to rapidly produce cytokines, such as interleukin 2 (IL-2), IL-4, and gamma interferon (IFN-γ) in response to infections by viruses, bacteria, and parasites. The bacterial superantigen staphylococcal enterotoxin B (SEB) interacts with T cells bearing the Vβ3, -7, or -8 T-cell receptors, inducing their expansion and cytokine secretion, leading to death in some cases due to cytokine poisoning. The majority of NKT cells bear the Vβ7 or -8 T-cell receptor, suggesting that they may play a role in regulating this response. Using mice lacking NKT cells (CD1d−/− and Jα18−/− mice), we set out to identify the role of these cells in T-cell expansion, cytokine secretion, and toxicity induced by exposure to SEB. We find that Vβ8+ CD4+ T-cell populations similarly expand in wild-type (WT) and NKT cell-null mice and that NKT cells did not regulate the secretion of IL-2. By contrast, these cells positively regulated the secretion of IL-4 and IFN-γ production and negatively regulated the secretion of tumor necrosis factor alpha (TNF-α). However, this negative regulation of TNF-α secretion by NKT cells provides only a minor protective effect on SEB-mediated shock in WT mice compared to mice lacking NKT cells. These data suggest that NKT cells may regulate the nature of the cytokine response to exposure to the superantigen SEB and may act as regulatory T cells during exposure to this superantigen.

Effects of Interferon Beta, Cyclophosphamide and Azathioprine on Cytokine Profile in Patients with Multiple Sclerosis

2005 ◽  
Vol 18 (2) ◽  
pp. 377-383 ◽  
Author(s):  
R. Totaro ◽  
A. Passacantando ◽  
T. Russo ◽  
I. Parzanese ◽  
M. Rascente ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Interleukin 2 ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Th2 Cytokines ◽  
Positive Interaction ◽  
Tnf Α ◽  
Ifn Γ

We assessed the in vitro effects of interferon beta-1b (IFNβ-1b), cyclophosphamide (CY), and azathioprine (AZA) alone and of the combination of IFNβ-1b with CY or AZA on the production of Th1 and Th2 cytokines in 10 patients with multiple sclerosis. Cytokine levels were determined at baseline and after stimulation with IFNβ-1b, CY, and AZA alone or with the combination of IFNβ-1b with CY or AZA. The combination of IFNβ-1b with CY resulted in a statistically significant decrease in the production of interleukin-2 (IL-2) (P=0.003) and tumor necrosis factor alfa (TNF-α) (P=0.03). An additive effect on the production of interferon gamma (IFN-γ) (P=0.2) and interleukin-10 (IL-10) (P=0.6), and a positive interaction on the production of interleukin-4 (IL-4) (P=0.08) were observed although the findings were not statistically significant. The combination of IFNβ-1b with AZA resulted in a significant negative effect on the production of IL-2 (P=0.006), whereas TNF-α (P=0.02), IFN-γ (P=0.03), IL-4 (P=0.2), and IL-10 (P=0.3) were not statistically impacted. Our data show that CY was able to improve the effects of IFNβ-1b on the ratio of Th1/Th2 cytokines.

scholarly journals Epstein-Barr Virus BZLF1-Mediated Downregulation of Proinflammatory Factors Is Essential for Optimal Lytic Viral Replication

2015 ◽  
Vol 90 (2) ◽  
pp. 887-903 ◽  
Author(s):  
Yuqing Li ◽  
Xubing Long ◽  
Lu Huang ◽  
Mengtian Yang ◽  
Yan Yuan ◽  
...  
Keyword(s):  
Viral Replication ◽  
Epstein Barr Virus ◽  
Lytic Cycle ◽  
Inflammatory Factors ◽  
Barr Virus ◽  
Ebv Infection ◽  
Tnf Α ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Proinflammatory Factors

ABSTRACTElevated secretion of inflammatory factors is associated with latent Epstein-Barr virus (EBV) infection and the pathology of EBV-associated diseases; however, knowledge of the inflammatory response and its biological significance during the lytic EBV cycle remains elusive. Here, we demonstrate that the immediate early transcriptional activator BZLF1 suppresses the proinflammatory factor tumor necrosis factor alpha (TNF-α) by binding to the promoter of TNF-α and preventing NF-κB activation. A BZLF1Δ207-210 mutant with a deletion of 4 amino acids (aa) in the protein-protein binding domain was not able to inhibit the proinflammatory factors TNF-α and gamma interferon (IFN-γ) and reduced viral DNA replication with complete transcriptional activity during EBV lytic gene expression. TNF-α depletion restored the viral replication mediated by BZLF1Δ207-210. Furthermore, a combination of TNF-α- and IFN-γ-neutralizing antibodies recovered BZLF1Δ207-210-mediated viral replication, indicating that BZLF1 attenuates the antiviral response to aid optimal lytic replication primarily through the inhibition of TNF-α and IFN-γ secretion during the lytic cycle. These results suggest that EBV BZLF1 attenuates the proinflammatory responses to facilitate viral replication.IMPORTANCEThe proinflammatory response is an antiviral and anticancer strategy following the complex inflammatory phenotype. Latent Epstein-Barr virus (EBV) infection strongly correlates with an elevated secretion of inflammatory factors in a variety of severe diseases, while the inflammatory responses during the lytic EBV cycle have not been established. Here, we demonstrate that BZLF1 acts as a transcriptional suppressor of the inflammatory factors TNF-α and IFN-γ and confirm that BZLF1-facilitated escape from the TNF-α and IFN-γ response during the EBV lytic life cycle is required for optimal viral replication. This finding implies that the EBV lytic cycle employs a distinct strategy to evade the antiviral inflammatory response.

The human Clara cell protein: biochemical and biological characterisation of a natural immunosuppressor

1996 ◽  
Vol 1 (6) ◽  
pp. 385-387 ◽  
Author(s):  
I Dierynck ◽  
A Bernard ◽  
H Roels ◽  
M DeLey
Keyword(s):  
Clara Cell ◽  
Cell Protein ◽  
Cytokine Network ◽  
Inflammatory Reactions ◽  
Clara Cell Protein ◽  
Tnf Α ◽  
Human Counterpart ◽  
Ifn Γ ◽  
Rabbit Uteroglobin ◽  
Inflammatory Action

The Clara cell protein, the human counterpart of rabbit uteroglobin, exerts an anti-inflammatory action by interfering in different ways with the cytokine-network. Firstly, CC16 behaves like an anti-cytokine by downregulating the production of IFN-γ, IL-1 and TNF-α by stimulated leukocytes. The extent of inhibition depends on the inducing agent (being maximal when IL-2 is used as inducer) and varies with the applied concentration of CC16. Secondly, the protein reduces the antiviral activity and the augmentation of phagocytosis induced by IFN-γ. In both cases (inhibition of production and biologic activity) there is a 50% reduction in the presence of 10 ng/ml CC16. The natural and IFN-γ-enduced cytotoxicity of NK-cells however, are enhanced by the presence of CC16, indicating a more complex interaction of CC16 with the immune-system. The immunosuppressive properties make CC16 a promising agent for the treatment of inflammatory reactions and auto-immune diseases.

scholarly journals Comparison of Serum and Cell-Specific Cytokines in Humans

2001 ◽  
Vol 8 (6) ◽  
pp. 1097-1103 ◽  
Author(s):  
Janine Jason ◽  
Lennox K. Archibald ◽  
Okey C. Nwanyanwu ◽  
Martha G. Byrd ◽  
Peter N. Kazembe ◽  
...  
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Cell ◽  
Necrosis Factor Alpha ◽  
Entire Study ◽  
Serum Cytokines ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Ifn Γ

ABSTRACT Cytokines function at the cellular, microenvironmental level, but human cytokine assessment is most commonly done at the macro level, by measuring serum cytokines. The relationships between serum and cellular cytokines, if there are any, are undefined. In a study of hospitalized patients in Malawi, we compared cytometrically assessed, cell-specific cytokine data to serum interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) levels in 16 children and 71 (IL-2, -4, -6, -10) or 159 (IL-8, IFN-γ, and TNF-α) adults, using Wilcoxon rank sum tests and Pearson's (rp ) and Spearman's (rs ) rank correlations. For the entire study group, correlations between identical serum and cellular cytokines mainly involved IL-8 and IFN-γ, were few, and were weakly positive (r < 0.40). Blood culture-positive persons had the most and strongest correlations, including those between serum IL-2 levels and the percentages of lymphocytes spontaneously making IL-2 (rs = +0.74), serum IL-8 levels and the percentages of lymphocytes spontaneously making IL-8 (rp = +0.66), and serum IL-10 levels and the percentages of CD8+ T cells making TNF-α (rp = +0.89). Human immunodeficiency virus (HIV)-positive persons had the next largest number of correlations, including several serum IL-8 level correlations, correlation of serum IL-10 levels with the percentages of lymphocytes producing induced IL-10 (rs = +0.36), and correlation of serum IFN-γ levels and the percentages of lymphocytes spontaneously making both IL-6 and IFN-γ in the same cell (rp = +0.59). HIV-negative, malaria smear-positive, and pediatric patients had few significant correlations; for the second and third of these subgroups, serum IL-8 level was correlated with the percentage of CD8− T cells producing induced IL-8 (rs = +0.40 and rs = +0.56, respectively). Thus, the strength of associations between serum and cellular cytokines varied with the presence or absence of bloodstream infection, HIV status, and perhaps other factors we did not assess. These results strongly suggest that serum cytokines at best only weakly reflect peripheral blood cell cytokine production and balances.

Sign in / Sign up

Export Citation Format

Share Document