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  • Title: Soluble vascular endothelial growth factor receptor-1 protects mice in sepsis.
    Author: Tsao PN, Chan FT, Wei SC, Hsieh WS, Chou HC, Su YN, Chen CY, Hsu WM, Hsieh FJ, Hsu SM.
    Journal: Crit Care Med; 2007 Aug; 35(8):1955-60. PubMed ID: 17568329.
    Abstract:
    OBJECTIVE: To determine the putative role in the modulation of inflammation of a soluble form of Flt-1 (sFlt), a potent vascular endothelial growth factor antagonist, in experimental endotoxemia and sepsis. DESIGN: Randomized prospective experimental study. SETTING: University medical laboratory. SUBJECTS: Male C56BL/6 strain mice. INTERVENTIONS: We investigated the expression patterns and the effects of vascular endothelial growth factor and soluble Flt-1 in experimental endotoxic shock and sepsis. The possible anti-inflammatory mechanism of soluble Flt-1 was also evaluated. MEASUREMENTS AND MAIN RESULTS: Both vascular endothelial growth factor and sFlt-1 were rapidly released from macrophages activated in vitro by lipopolysaccharide and in the plasma of endotoxemic mice. Administration of vascular endothelial growth factor enhanced proinflammatory cytokine production and mediated a dramatic increase in mortality in endotoxemic mice. Treatment with sFlt-1 attenuated inflammatory responses, inhibited recruitment of inflammatory cells into the peritoneal cavity, and improved survival in a lethal endotoxemia and cecal ligation and puncture-induced sepsis model, even when administered as late as 24 hrs after the onset of sepsis. CONCLUSIONS: These findings support a critical protective role of sFlt-1 in endotoxic shock and sepsis. sFlt-1 may therefore have utility as an adjunctive agent for the treatment of sepsis syndrome.
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