Cargando…

An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models

BACKGROUND: The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A(2A )adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis. METHODS: Sepsis was induced in mice by i...

Descripción completa

Detalles Bibliográficos
Autores principales: Moore, Christopher C, Martin, Edward N, Lee, Grace H, Obrig, Tom, Linden, Joel, Scheld, W Michael
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588444/
https://www.ncbi.nlm.nih.gov/pubmed/18937852
http://dx.doi.org/10.1186/1471-2334-8-141
_version_ 1782160932841979904
author Moore, Christopher C
Martin, Edward N
Lee, Grace H
Obrig, Tom
Linden, Joel
Scheld, W Michael
author_facet Moore, Christopher C
Martin, Edward N
Lee, Grace H
Obrig, Tom
Linden, Joel
Scheld, W Michael
author_sort Moore, Christopher C
collection PubMed
description BACKGROUND: The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A(2A )adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis. METHODS: Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A(2A )AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days. RESULTS: There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-α, MIP-1α, MCP-1, IFN-γ, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01). CONCLUSION: Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.
format Text
id pubmed-2588444
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-25884442008-11-27 An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models Moore, Christopher C Martin, Edward N Lee, Grace H Obrig, Tom Linden, Joel Scheld, W Michael BMC Infect Dis Research Article BACKGROUND: The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A(2A )adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis. METHODS: Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A(2A )AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days. RESULTS: There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-α, MIP-1α, MCP-1, IFN-γ, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01). CONCLUSION: Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis. BioMed Central 2008-10-20 /pmc/articles/PMC2588444/ /pubmed/18937852 http://dx.doi.org/10.1186/1471-2334-8-141 Text en Copyright © 2008 Moore et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Moore, Christopher C
Martin, Edward N
Lee, Grace H
Obrig, Tom
Linden, Joel
Scheld, W Michael
An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
title An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
title_full An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
title_fullStr An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
title_full_unstemmed An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
title_short An A(2A )adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models
title_sort a(2a )adenosine receptor agonist, atl313, reduces inflammation and improves survival in murine sepsis models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588444/
https://www.ncbi.nlm.nih.gov/pubmed/18937852
http://dx.doi.org/10.1186/1471-2334-8-141
work_keys_str_mv AT moorechristopherc ana2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT martinedwardn ana2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT leegraceh ana2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT obrigtom ana2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT lindenjoel ana2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT scheldwmichael ana2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT moorechristopherc a2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT martinedwardn a2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT leegraceh a2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT obrigtom a2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT lindenjoel a2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels
AT scheldwmichael a2aadenosinereceptoragonistatl313reducesinflammationandimprovessurvivalinmurinesepsismodels