title: Inhibition of infection-mediated preterm birth by administration of broad spectrum chemokine inhibitor in mice.
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.
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada.
authors.forename: Oksana
authors.initials: O
authors.lastname: Shynlova
authors.forename: Anna
authors.initials: A
authors.lastname: Dorogin
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Li
authors.forename: Stephen
authors.initials: S
authors.lastname: Lye
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008813:Mice, Inbred ICR; D009215:Myometrium / Q000187:drug effects / Q000276:immunology; D020556:Neutrophil Infiltration; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D047928:Premature Birth / Q000276:immunology / Q000517:prevention & control*; D014599:Uterus / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D008070:Lipopolysaccharides
keywords: chemokine inhibitor; infection; leucocyte infiltration; preterm labour; uterus