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

Research output: Contribution to journalJournal articlepeer-review

Standard

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-Bojsoe, Christine; Esmann Fonvig, Cilius; Holm, Jens-Christian; Hansen, Torben; Holst, Jens Juul; Müller, Klaus Gottlob.

In: Frontiers in Immunology, Vol. 12, 2021.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Ebbesen, M, Kissow, H, Hartmann, B, Kielsen, K, Sørensen, K, Stinson, SE, Frithioff-Bojsoe, C, Esmann Fonvig, C, Holm, J-C, Hansen, T, Holst, JJ & Müller, KG 2021, 'Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation', Frontiers in Immunology, vol. 12. https://doi.org/10.3389/fimmu.2021.793588

APA

Ebbesen, M., Kissow, H., Hartmann, B., Kielsen, K., Sørensen, K., Stinson, S. E., Frithioff-Bojsoe, C., Esmann Fonvig, C., Holm, J-C., Hansen, T., Holst, J. J., & Müller, K. G. (2021). Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.793588

Vancouver

Ebbesen M, Kissow H, Hartmann B, Kielsen K, Sørensen K, Stinson SE et al. Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation. Frontiers in Immunology. 2021;12. https://doi.org/10.3389/fimmu.2021.793588

Author

Ebbesen, Maria ; Kissow, Hannelouise ; Hartmann, Bolette ; Kielsen, Katrine ; Sørensen, Kaspar ; Stinson, Sara Elizabeth ; Frithioff-Bojsoe, 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. In: Frontiers in Immunology. 2021 ; Vol. 12.

Bibtex

@article{db60158de4bb4e5fa430651194a2eb11,
title = "Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation",
abstract = "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.",
keywords = "hematopoietic stem cell transplantation, high-dose chemotherapy, glucagon-like peptide-1, toxicity, systemic inflammation, pediatrics, growth factors",
author = "Maria Ebbesen and Hannelouise Kissow and Bolette Hartmann and Katrine Kielsen and Kaspar S{\o}rensen and Stinson, {Sara Elizabeth} and Christine Frithioff-Bojsoe and {Esmann Fonvig}, Cilius and Jens-Christian Holm and Torben Hansen and Holst, {Jens Juul} and M{\"u}ller, {Klaus Gottlob}",
year = "2021",
doi = "10.3389/fimmu.2021.793588",
language = "English",
volume = "12",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Glucagon-Like Peptide-1 Is Associated With Systemic Inflammation in Pediatric Patients Treated With Hematopoietic Stem Cell Transplantation

AU - Ebbesen, Maria

AU - Kissow, Hannelouise

AU - Hartmann, Bolette

AU - Kielsen, Katrine

AU - Sørensen, Kaspar

AU - Stinson, Sara Elizabeth

AU - Frithioff-Bojsoe, Christine

AU - Esmann Fonvig, Cilius

AU - Holm, Jens-Christian

AU - Hansen, Torben

AU - Holst, Jens Juul

AU - Müller, Klaus Gottlob

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - hematopoietic stem cell transplantation

KW - high-dose chemotherapy

KW - glucagon-like peptide-1

KW - toxicity

KW - systemic inflammation

KW - pediatrics

KW - growth factors

U2 - 10.3389/fimmu.2021.793588

DO - 10.3389/fimmu.2021.793588

M3 - Journal article

C2 - 34956226

VL - 12

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -

ID: 288273082