Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia

Ofer Yanay,1,2 Adam L Bailey,3 Kelly Kernan,1 Jerry J Zimmerman,1,2 William R Osborne1 1Department of Pediatrics, University of Washington, 2Division of Pediatric Critical Care Medicine, Seattle Children's Hospital, Seattle, WA, 3Medical Scientist Training Program, University of Wisconsin, M...

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Autores principales:	Yanay O, Bailey AL, Kernan K, Zimmerman JJ, Osborne WR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a4c5845905644ce49a15c40768af070b
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spelling	oai:doaj.org-article:a4c5845905644ce49a15c40768af070b2021-12-02T03:08:16ZEffects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia1178-7031https://doaj.org/article/a4c5845905644ce49a15c40768af070b2015-07-01T00:00:00Zhttp://www.dovepress.com/effects-of-exendin-4-a-glucagon-like-peptide-1-receptor-agonist-on-neu-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Ofer Yanay,1,2 Adam L Bailey,3 Kelly Kernan,1 Jerry J Zimmerman,1,2 William R Osborne1 1Department of Pediatrics, University of Washington, 2Division of Pediatric Critical Care Medicine, Seattle Children's Hospital, Seattle, WA, 3Medical Scientist Training Program, University of Wisconsin, Madison, WI, USA Background: Sepsis remains a major cause of morbidity and mortality. A variety of strategies targeting modulation of the pro-inflammatory response associated with early sepsis have been reported without clinical success. GLP-1 enhances glucose-stimulated insulin secretion. In addition, it was shown to have anti-inflammatory effects. We hypothesized that treatment with exendin-4, a GLP-1 receptor agonist, would attenuate inflammation and improve glucose control in a lipopolysaccharide (LPS) rat model of inflammation. Methods: Two-month-old male Wistar rats were randomly assigned to one of the following four groups: 1) treatment: intraperitoneal (IP) injection of LPS 10 mg/kg followed by exendin-4, 30 µg/kg, 10 minutes later; 2) control-1: IP injection of LPS 10 mg/kg, followed by normal saline (NS); 3) control-2: IP NS injection followed by exendin-4; 4) sham: IP injection of NS followed by another NS injection. Glucose concentration, total white blood count with absolute neutrophil count, and pro- and anti-inflammatory cytokine concentrations were measured at 0, 3, 6, and 10 hours following LPS injection. Results: At 3 hours, rats injected with LPS developed neutropenia, elevated pro- and anti-inflammatory cytokines, and mild hypoglycemia. Treatment with exendin-4 significantly modulated neutropenia, and decreased pro-inflammatory cytokine concentrations (IL-1α, IL-1β, IL-6, TNFα, and IFNγ). However, exendin-4 had no effect on IL-10 concentrations. LPS injection led to mild hypoglycemia, that was not observed in rats treated with exendin-4. Sham animals exhibited no significant change from baseline in all parameters. Conclusion: In this LPS model of acute early phase inflammation, treatment with exendin-4 decreased pro-inflammatory cytokine concentrations without changing IL-10 blood levels and improved neutropenia. Following LPS injection, rats developed a tendency toward hypoglycemia that improved with exendin-4. Overall our data suggest that exogenous exendin-4 mediates anti-inflammatory effects early in this rat model of endotoxin-induced inflammation. Keywords: glucagon like peptide-1, exendin-4, sepsis, endotoxemia, inflammation, neutrophilsYanay OBailey ALKernan KZimmerman JJOsborne WRDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2015, Iss default, Pp 129-135 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Yanay O Bailey AL Kernan K Zimmerman JJ Osborne WR Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia
description	Ofer Yanay,1,2 Adam L Bailey,3 Kelly Kernan,1 Jerry J Zimmerman,1,2 William R Osborne1 1Department of Pediatrics, University of Washington, 2Division of Pediatric Critical Care Medicine, Seattle Children's Hospital, Seattle, WA, 3Medical Scientist Training Program, University of Wisconsin, Madison, WI, USA Background: Sepsis remains a major cause of morbidity and mortality. A variety of strategies targeting modulation of the pro-inflammatory response associated with early sepsis have been reported without clinical success. GLP-1 enhances glucose-stimulated insulin secretion. In addition, it was shown to have anti-inflammatory effects. We hypothesized that treatment with exendin-4, a GLP-1 receptor agonist, would attenuate inflammation and improve glucose control in a lipopolysaccharide (LPS) rat model of inflammation. Methods: Two-month-old male Wistar rats were randomly assigned to one of the following four groups: 1) treatment: intraperitoneal (IP) injection of LPS 10 mg/kg followed by exendin-4, 30 µg/kg, 10 minutes later; 2) control-1: IP injection of LPS 10 mg/kg, followed by normal saline (NS); 3) control-2: IP NS injection followed by exendin-4; 4) sham: IP injection of NS followed by another NS injection. Glucose concentration, total white blood count with absolute neutrophil count, and pro- and anti-inflammatory cytokine concentrations were measured at 0, 3, 6, and 10 hours following LPS injection. Results: At 3 hours, rats injected with LPS developed neutropenia, elevated pro- and anti-inflammatory cytokines, and mild hypoglycemia. Treatment with exendin-4 significantly modulated neutropenia, and decreased pro-inflammatory cytokine concentrations (IL-1α, IL-1β, IL-6, TNFα, and IFNγ). However, exendin-4 had no effect on IL-10 concentrations. LPS injection led to mild hypoglycemia, that was not observed in rats treated with exendin-4. Sham animals exhibited no significant change from baseline in all parameters. Conclusion: In this LPS model of acute early phase inflammation, treatment with exendin-4 decreased pro-inflammatory cytokine concentrations without changing IL-10 blood levels and improved neutropenia. Following LPS injection, rats developed a tendency toward hypoglycemia that improved with exendin-4. Overall our data suggest that exogenous exendin-4 mediates anti-inflammatory effects early in this rat model of endotoxin-induced inflammation. Keywords: glucagon like peptide-1, exendin-4, sepsis, endotoxemia, inflammation, neutrophils
format	article
author	Yanay O Bailey AL Kernan K Zimmerman JJ Osborne WR
author_facet	Yanay O Bailey AL Kernan K Zimmerman JJ Osborne WR
author_sort	Yanay O
title	Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia
title_short	Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia
title_full	Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia
title_fullStr	Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia
title_full_unstemmed	Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia
title_sort	effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/a4c5845905644ce49a15c40768af070b
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Effects of exendin-4, a glucagon like peptide-1 receptor agonist, on neutrophil count and inflammatory cytokines in a rat model of endotoxemia

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