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Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged with severe side effects, which are propagated by mucosal barrier disruption, and the related microbial translocation and systemic inflammation. Glucagon-like peptide-1 (GLP-1), a well-known incretin hormone...

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Autores principales: Ebbesen, Maria, Kissow, Hannelouise, Hartmann, Bolette, Kielsen, Katrine, Sørensen, Kaspar, Stinson, Sara Elizabeth, Frithioff-Bøjsøe, Christine, Esmann Fonvig, Cilius, Holm, Jens-Christian, Hansen, Torben, Holst, Jens Juul, Müller, Klaus Gottlob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692255/
https://www.ncbi.nlm.nih.gov/pubmed/34956226
http://dx.doi.org/10.3389/fimmu.2021.793588
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author Ebbesen, Maria
Kissow, Hannelouise
Hartmann, Bolette
Kielsen, Katrine
Sørensen, Kaspar
Stinson, Sara Elizabeth
Frithioff-Bøjsøe, Christine
Esmann Fonvig, Cilius
Holm, Jens-Christian
Hansen, Torben
Holst, Jens Juul
Müller, Klaus Gottlob
author_facet Ebbesen, Maria
Kissow, Hannelouise
Hartmann, Bolette
Kielsen, Katrine
Sørensen, Kaspar
Stinson, Sara Elizabeth
Frithioff-Bøjsøe, Christine
Esmann Fonvig, Cilius
Holm, Jens-Christian
Hansen, Torben
Holst, Jens Juul
Müller, Klaus Gottlob
author_sort Ebbesen, Maria
collection PubMed
description Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged with severe side effects, which are propagated by mucosal barrier disruption, and the related microbial translocation and systemic inflammation. Glucagon-like peptide-1 (GLP-1), a well-known incretin hormone, possesses anti-inflammatory properties and promotes regeneration of damaged intestinal epithelium in animal studies. We hypothesized that the immense inter-individual variation in the degree of mucosal damage and systemic inflammation, seen after HSCT is influenced by endogenous GLP-1 and could be related to acute post-transplant complications. In this prospective study we measured serial weekly fasting plasma GLP-1, along with C-reactive protein (CRP), and citrulline in 82 pediatric patients during allogeneic HSCT together with a fasting plasma GLP-1 in sex- and age-matched healthy controls. Overall, GLP-1 levels were increased in the patients during the course of HSCT compared with the controls, but tended to decrease post-transplant, most pronounced in patients receiving high-intensity conditioning regimen. The increase in CRP seen in the early post-transplant phase was significantly lower from day +8 to +13 in patients with GLP-1 above the upper quartile (>10 pmol/L) at day 0 (all P ≤ 0.03). Similar findings were seen for peak CRP levels after adjusting for type of conditioning (-47.0%; 95% CI, -8.1 – -69.4%, P = 0.02). Citrulline declined significantly following the transplantation illustrating a decrease in viable enterocytes, most evident in patients receiving high-intensity conditioning regimen. GLP-1 levels at day 0 associated with the recovery rate of citrulline from day 0 to +21 (34 percentage points (pp)/GLP-1 doubling; 95% CI, 10 – 58pp; P = 0. 008) and day 0 to day +90 (48 pp/GLP-1 doubling; 95% CI, 17 – 79pp; P = 0. 004), also after adjustment for type of conditioning. This translated into a reduced risk of acute graft-versus-host disease (aGvHD) in patients with highest day 0 GLP-1 levels (>10 pmol/L) (cause-specific HR: 0.3; 95% CI, 0.2 – 0.9, P = 0.02). In conclusion, this study strongly suggests that GLP-1 influences regeneration of injured epithelial barriers and ameliorates inflammatory responses in the early post-transplant phase.
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spelling pubmed-86922552021-12-23 Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation Ebbesen, Maria Kissow, Hannelouise Hartmann, Bolette Kielsen, Katrine Sørensen, Kaspar Stinson, Sara Elizabeth Frithioff-Bøjsøe, Christine Esmann Fonvig, Cilius Holm, Jens-Christian Hansen, Torben Holst, Jens Juul Müller, Klaus Gottlob Front Immunol Immunology Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged with severe side effects, which are propagated by mucosal barrier disruption, and the related microbial translocation and systemic inflammation. Glucagon-like peptide-1 (GLP-1), a well-known incretin hormone, possesses anti-inflammatory properties and promotes regeneration of damaged intestinal epithelium in animal studies. We hypothesized that the immense inter-individual variation in the degree of mucosal damage and systemic inflammation, seen after HSCT is influenced by endogenous GLP-1 and could be related to acute post-transplant complications. In this prospective study we measured serial weekly fasting plasma GLP-1, along with C-reactive protein (CRP), and citrulline in 82 pediatric patients during allogeneic HSCT together with a fasting plasma GLP-1 in sex- and age-matched healthy controls. Overall, GLP-1 levels were increased in the patients during the course of HSCT compared with the controls, but tended to decrease post-transplant, most pronounced in patients receiving high-intensity conditioning regimen. The increase in CRP seen in the early post-transplant phase was significantly lower from day +8 to +13 in patients with GLP-1 above the upper quartile (>10 pmol/L) at day 0 (all P ≤ 0.03). Similar findings were seen for peak CRP levels after adjusting for type of conditioning (-47.0%; 95% CI, -8.1 – -69.4%, P = 0.02). Citrulline declined significantly following the transplantation illustrating a decrease in viable enterocytes, most evident in patients receiving high-intensity conditioning regimen. GLP-1 levels at day 0 associated with the recovery rate of citrulline from day 0 to +21 (34 percentage points (pp)/GLP-1 doubling; 95% CI, 10 – 58pp; P = 0. 008) and day 0 to day +90 (48 pp/GLP-1 doubling; 95% CI, 17 – 79pp; P = 0. 004), also after adjustment for type of conditioning. This translated into a reduced risk of acute graft-versus-host disease (aGvHD) in patients with highest day 0 GLP-1 levels (>10 pmol/L) (cause-specific HR: 0.3; 95% CI, 0.2 – 0.9, P = 0.02). In conclusion, this study strongly suggests that GLP-1 influences regeneration of injured epithelial barriers and ameliorates inflammatory responses in the early post-transplant phase. Frontiers Media S.A. 2021-12-08 /pmc/articles/PMC8692255/ /pubmed/34956226 http://dx.doi.org/10.3389/fimmu.2021.793588 Text en Copyright © 2021 Ebbesen, Kissow, Hartmann, Kielsen, Sørensen, Stinson, Frithioff-Bøjsøe, Esmann Fonvig, Holm, Hansen, Holst and Müller https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ebbesen, Maria
Kissow, Hannelouise
Hartmann, Bolette
Kielsen, Katrine
Sørensen, Kaspar
Stinson, Sara Elizabeth
Frithioff-Bøjsøe, Christine
Esmann Fonvig, Cilius
Holm, Jens-Christian
Hansen, Torben
Holst, Jens Juul
Müller, Klaus Gottlob
Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation
title Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation
title_full Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation
title_fullStr Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation
title_full_unstemmed Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation
title_short Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation
title_sort glucagon-like peptide-1 is associated with systemic inflammation in pediatric patients treated with hematopoietic stem cell transplantation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692255/
https://www.ncbi.nlm.nih.gov/pubmed/34956226
http://dx.doi.org/10.3389/fimmu.2021.793588
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