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

J Cell Mol Med. 2014 Sep;18(9):1816-29. doi: 10.1111/jcmm.12307. Epub 2014 Jun 4.


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.

Keywords: chemokine inhibitor; infection; leucocyte infiltration; preterm labour; uterus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Chemokines / antagonists & inhibitors*
  • Chemokines / genetics
  • Chemokines / metabolism
  • Female
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mice, Inbred ICR
  • Myometrium / drug effects
  • Myometrium / immunology
  • Neutrophil Infiltration
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Premature Birth / immunology
  • Premature Birth / prevention & control*
  • Uterus / drug effects
  • Uterus / immunology


  • Anti-Inflammatory Agents
  • Chemokines
  • Lipopolysaccharides