Block of Granulocyte-Macrophage Colony-Stimulating Factor Prevents Inflammation-Induced Preterm Birth in a Mouse Model for Parturition. (April 2019)

• Record Type: Journal Article
• Authors: Nold, Christopher; Stone, Julie; O'Hara, Kathleen; Davis, Patricia; Kiveliyk, Vladislav; Blanchard, Vanessa; Yellon, Steven M.; Vella, Anthony T.
• Is Part Of: Reproductive sciences. Volume 26:Number 4(2019:Apr.)
• Page Start: 551
• Page End: 559
• Publication Date: 2019-04
• Subjects: preterm birth -- cervical remodeling -- inflammation; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719118804420
• Languages: English
• ISSNs: 1933-7191

Abstract

Objective: A multitude of factors promotes inflammation in the reproductive tract leading to preterm birth. Macrophages peak in the cervix prior to birth and their numbers are increased by the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We hypothesize GM-CSF is produced from multiple sites in the genital tract and is a key mediator in preterm birth. Study Design: Ectocervical, endocervical, and amniotic fluid mesenchymal stem cells were treated with lipopolysaccharide (LPS), and the concentration and expression of GM-CSF was measured. Pregnant CD-1 mice on gestational day 17 received LPS and an intravenous injection of either anti-mouse GM-CSF or control antibody. After 6 hours, the preterm birth rate was recorded. Results: Treatment with LPS increased the GM-CSF concentration and messenger RNA expression after 24 hours in all 3 cell lines ( P < .01). Mice treated with LPS and the GM-CSF antibody had a preterm birth rate of 25%, compared to a 66.7% preterm birth rate in controls, within 6 hours ( P < .05, χ 2 ). Treatment with the anti-mouse GM-CSF antibody decreased the concentration of GM-CSF in the mouse serum ( P < .01) but did not alter the number of macrophages or collagen content in the cervix. Conclusion: These studies demonstrate that GM-CSF is produced from multiple sites in the genital tract and that treatment with an antibody to GM-CSF prevents preterm birth. Curiously, the anti-mouse GM-CSF antibody did not decrease the number of macrophages in the cervix. Further research is needed to determine whether antibodies to GM-CSF can be utilized as a therapeutic agent to prevent preterm birth.