Inhibition of infection-mediated preterm birth by administration of broad spectrum chemokine inhibitor in mice

Authors

  • Oksana Shynlova,

    Corresponding author
    1. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    2. Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada
    • Correspondence to: Dr. Oksana SHYNLOVA,

      Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital,

      25 Orde Street, Suite 6-1019, Toronto, ON,

      Canada M5G 1X5.

      Tel.: 416-586-4800, ext 8631

      Fax: 416-586-5116

      E-mail: shynlova@lunenfeld.ca

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  • Anna Dorogin,

    1. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
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  • Yunqing Li,

    1. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    2. Department of Physiology, University of Toronto, Toronto, ON, Canada
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  • Stephen Lye

    1. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    2. Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada
    3. Department of Physiology, University of Toronto, Toronto, ON, Canada
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Abstract

Preterm birth (PTB) is the single most important cause of perinatal and infant mortality worldwide. Maternal infection can result in PTB. We investigated the ability of a Broad Spectrum Chemokine Inhibitor (BSCI) to prevent infection-induced PTB in mice. PTB was initiated in pregnant mice by intraperitoneal injection of lipopolysaccharide (LPS; 50 μg). Half the mice received BSCI (10 mg/kg) 24 hrs prior to and immediately before LPS administration. The impact of LPS alone or LPS plus BSCI was assessed on (i) injection-to-delivery interval, foetal survival rate, placental and neonates' weight; (ii) amniotic fluid and maternal plasma cytokine levels (by Luminex assay); foetal and maternal tissue cytokine gene expression levels (by Real-Time RT-PCR); (iii) immune cells infiltration into the uterine tissue (by stereological immunohistochemistry). Pre-treatment with BSCI (i) decreased LPS-induced PTB (64% versus 100%, P < 0.05); (ii) significantly attenuated cytokine/chemokine expression in maternal tissues (plasma, liver, myometrium, decidua); (iii) significantly decreased neutrophil infiltration in the mouse myometrium. BSCI-treated mice in which PTB was delayed till term had live foetuses with normal placental and foetal weight. BSCI represents a promising new class of therapeutics for PTB. In a mouse model of preterm labour, BCSI suppresses systemic inflammation in maternal tissues which resulted in the reduced incidence of LPS-mediated PTB. These data provide support for efforts to target inflammatory responses as a means of preventing PTB.

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