An A2Aadenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis modelsReportar como inadecuado




An A2Aadenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Infectious Diseases

, 8:141

First Online: 20 October 2008Received: 09 June 2008Accepted: 20 October 2008

Abstract

BackgroundThe pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A2A adenosine receptor AR agonist treated and untreated animals during experimental sepsis.

MethodsSepsis 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 A2A 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.

ResultsThere 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.

ConclusionFurther studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2334-8-141 contains supplementary material, which is available to authorized users.

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Autor: Christopher C Moore - Edward N Martin - Grace H Lee - Tom Obrig - Joel Linden - W Michael Scheld

Fuente: https://link.springer.com/







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