Gastrin-releasing Peptide Receptor Antagonist Effects on an Animal Model of Sepsis

• DOI: 10.1164/rccm.200507-1118oc
• Publication Date: 2005-09-29T00:34:12Z
• Authors: Felipe Dal-Pizzol; Luciane Pons Di L...; Cristiane Ritter; Márcio Rodrigo Ma...; Adalisa Reinke; Daniel Pens Gelain; Alfeu Zanotto-Filho; Luiz Fernando de ...; Michael Andrades; Denise Frediani B...; Elena Aida Bernard; Martin Cammarota; Lia R. M. Bevilaqua; Francisco Garcia ...; José Cláudio; Fonseca Moreira; Rafael Roesler; Gilberto Schwarts...
• Keywords: Proinflammatory cytokine; Gastrin-releasing peptide

Several new therapeutic strategies have been described for the treatment of sepsis, but to date none are related alterations in bombesin/gastrin-releasing peptide (GRP) receptor pathways.To determine effects a selective GRP antagonist, RC-3095, on cytokine release from macrophages and its vivo cecal ligation puncture (CLP) model sepsis acute lung injury induced by intratracheal instillation LPS.We determined RC-3095 CLP LPS. In addition, we tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, nitric oxide activated macrophages.The antagonist attenuated LPS- or CLP-induced TNF-alpha, IL-1beta, cultured decreased mRNA levels inducible synthase. The administration (0.3 mg/kg) 6 h after induction improved survival model, diminished damage These were associated with attenuation circulating TNF-alpha IL-1beta myeloperoxidase activity several organs.We report that attenuates proinflammatory cytokines vitro improves "established" sepsis. consistent involvement inflammatory pathway relevant development