Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid

Abstract Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For...

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Autores principales:	Rebecca Herzog, Lilian Kuster, Julia Becker, Tobias Gluexam, Dietmar Pils, Andreas Spittler, Manoj K. Bhasin, Seth L. Alper, Andreas Vychytil, Christoph Aufricht, Klaus Kratochwill
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9cfa7994a28245e394ea579d9e00800f
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spelling	oai:doaj.org-article:9cfa7994a28245e394ea579d9e00800f2021-12-02T16:06:41ZFunctional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid10.1038/s41598-017-05872-22045-2322https://doaj.org/article/9cfa7994a28245e394ea579d9e00800f2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05872-2https://doaj.org/toc/2045-2322Abstract Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.Rebecca HerzogLilian KusterJulia BeckerTobias GluexamDietmar PilsAndreas SpittlerManoj K. BhasinSeth L. AlperAndreas VychytilChristoph AufrichtKlaus KratochwillNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rebecca Herzog Lilian Kuster Julia Becker Tobias Gluexam Dietmar Pils Andreas Spittler Manoj K. Bhasin Seth L. Alper Andreas Vychytil Christoph Aufricht Klaus Kratochwill Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
description	Abstract Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.
format	article
author	Rebecca Herzog Lilian Kuster Julia Becker Tobias Gluexam Dietmar Pils Andreas Spittler Manoj K. Bhasin Seth L. Alper Andreas Vychytil Christoph Aufricht Klaus Kratochwill
author_facet	Rebecca Herzog Lilian Kuster Julia Becker Tobias Gluexam Dietmar Pils Andreas Spittler Manoj K. Bhasin Seth L. Alper Andreas Vychytil Christoph Aufricht Klaus Kratochwill
author_sort	Rebecca Herzog
title	Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
title_short	Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
title_full	Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
title_fullStr	Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
title_full_unstemmed	Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
title_sort	functional and transcriptomic characterization of peritoneal immune-modulation by addition of alanyl-glutamine to dialysis fluid
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9cfa7994a28245e394ea579d9e00800f
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Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid

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