Effect of Increased Convection Volume by Mid-Dilution Hemodiafiltration on the Subclinical Chronic Inflammation in Maintenance Hemodialysis Patients

2018 ◽  
Vol 47 (1-3) ◽  
pp. 1-9 ◽  
Author(s):  
Silvio Borrelli ◽  
Roberto Minutolo ◽  
Emanuele De Simone ◽  
Walter De Simone ◽  
MIchele Provenzano ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Chronic Hemodialysis ◽  
Maintenance Hemodialysis ◽  
Reactive Protein ◽  
Inflammatory Pattern ◽  
Factor Α ◽  
Convective Volume ◽  
Necrosis Factor

Mid-dilution hemodiafiltration (MID) is a dialytic technique that might improve systemic inflammation of patients in chronic hemodialysis (HD) by increasing substitution volumes. To verify this hypothesis, we performed a prospective cross-over study comparing the effect on inflammatory biomarkers of higher convection by MID versus standard convection by post-dilution hemodiafiltration (HDF). Patients under chronic HD were therefore treated by MID and HDF by crossover design. Each treatment period lasted 4 months, with 1 month of wash-out where patients were treated by HD, for a total of 9 months. Primary outcome was the change of serum pre-dialytic C-Reactive Protein (CRP), interleukin 6 (IL-6), IL-1, IL-10, transforming growth factor-β (TGF-β), tumor necrosis factor-α, albumin and pre-albumin. Samples were obtained monthly. Ten HD patients were enrolled (age: 64.9 ± 12.6 years; 70% males; dialytic vintage: 10.6 [2.7–16.2] years). Mean convection volume was 40.1 ± 2.5 L/session in MID and 20.1 ± 2.6 L/session in HDF. A significant reduction of β2-Microglobulin was detected as a result of either treatment. In MID, CRP decreased from 11.3 (3.2–31.0) to 3.1 (1.4–14.4) mg/L (p = 0.007), IL-6 from 12.7 (5.0–29.7) to 8.3 (4.4–14.0) pg/mL (p = 0.003), and TGF-β from 10.6 (7.4–15.6) to 7.4 (5.9–9.3) ng/mL (p = 0.001). A significant reduction of CRP from 8.5 (3.2–31.0) to 4.6 (3.2–31.0) mg/L was also detected in HDF (p = 0.037), whereas no significant reduction of IL-6 (p = 0.147) and TGF-β (p = 0.094) was found. Percentage reduction of IL-6 correlated with mean convective volume in HDF (R = 0.666; p = 0.036) and in MID (R = 0.760; p = 0.020). Therefore, MID and HDF are associated with an attenuation of inflammatory pattern that is correlated with a high convective volume.

Exposure to febrile temperature modifies endothelial cell response to tumor necrosis factor-α

2001 ◽  
Vol 90 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Jeffrey D. Hasday ◽  
Douglas Bannerman ◽  
Sirhan Sakarya ◽  
Alan S. Cross ◽  
Ishwar S. Singh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Gm Csf ◽  
Tnf Α ◽  
Neutrophil Adherence ◽  
Endothelial Cell Response ◽  
Factor Α ◽  
Necrosis Factor

Fever is an important regulator of inflammation that modifies expression and bioactivity of cytokines, including tumor necrosis factor (TNF)-α. Pulmonary vascular endothelium is an important target of TNF-α during the systemic inflammatory response. In this study, we analyzed the effect of a febrile range temperature (39.5°C) on TNF-α-stimulated changes in endothelial barrier function, capacity for neutrophil binding and transendothelial migration (TEM), and cytokine secretion in human pulmonary artery endothelial cells (EC). Permeability for [14C]BSA tracer was increased by treatment with TNF-α, and this effect was augmented by incubating EC at 39.5°C. Treating EC with 2.5 U/ml TNF-α stimulated an increase in subsequent neutrophil adherence and TEM. Incubating EC at 39.5°C caused a 30% increase in TEM but did not modify the enhancement of neutrophil adherence or TEM by TNF-α treatment. Analysis of cytokine expression in EC cultures exposed to TNF-α at either 37° or 39.5°C revealed three patterns of temperature and TNF-α responsiveness. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-8 were not detectable in untreated EC but were increased after TNF-α exposure, and this increase was enhanced at 39.5°C. IL-6 expression was also increased with TNF-α exposure, but IL-6 expression was lower in 39.5°C EC cultures. Transforming growth factor-β1was constitutively expressed, and its expression was not influenced either by TNF-α or exposure to 39.5°C. These data demonstrate that clinically relevant shifts in body temperature might cause important changes in the effects of proinflammatory cytokines on the endothelium.

scholarly journals A mechanism of suppression of TGF–β/SMAD signaling by NF-κB/RelA

2000 ◽  
Vol 14 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Markus Bitzer ◽  
Gero von Gersdorff ◽  
Dan Liang ◽  
Alfredo Dominguez-Rosales ◽  
Amer A. Beg ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Transcriptional Responses ◽  
Smad Signaling ◽  
Antisense Mrna ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

A number of pathogenic and proinflammatory stimuli, and the transforming growth factor-β (TGF-β) exert opposing activities in cellular and immune responses. Here we show that the RelA subunit of nuclear factor κB (NF-κB/RelA) is necessary for the inhibition of TGF-β-induced phosphorylation, nuclear translocation, and DNA binding of SMAD signaling complexes by tumor necrosis factor-α (TNF-α). The antagonism is mediated through up-regulation of Smad7 synthesis and induction of stable associations between ligand-activated TGF-β receptors and inhibitory Smad7. Down-regulation of endogenous Smad7 by expression of antisense mRNA releases TGF-β/SMAD-induced transcriptional responses from suppression by cytokine-activated NF-κB/RelA. Following stimulation with bacterial lipopolysaccharide (LPS), or the proinflammatory cytokines TNF-α and interleukin-1β (IL-1β, NF-κB/RelA induces Smad7 synthesis through activation of Smad7 gene transcription. These results suggest a mechanism of suppression of TGF-β/SMAD signaling by opposing stimuli mediated through the activation of inhibitory Smad7 by NF-κB/RelA.

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