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Block of Granulocyte-Macrophage Colony-Stimulating Factor Prevents Inflammation-Induced Preterm Birth in a Mouse Model for Parturition

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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, χ2). 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.

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Authors and Affiliations

  1. Department of Women’s Health, Hartford Hospital, 85 Jefferson Street, Suite 625, Hartford, CT, 06102, USA

    Christopher Nold MD

  2. Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA

    Christopher Nold MD, Julie Stone MD, Kathleen O’Hara, Patricia Davis MD, Vladislav Kiveliyk & Anthony T. Vella PhD

  3. Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA

    Vanessa Blanchard & Steven M. Yellon PhD

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  1. Christopher Nold MD
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  2. Julie Stone MD
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  3. Kathleen O’Hara
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  4. Patricia Davis MD
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  5. Vladislav Kiveliyk
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  7. Steven M. Yellon PhD
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Correspondence to Christopher Nold MD.

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Authors’ Note

This research was conducted at the University of Connecticut School of Medicine in Farmington, Connecticut, and Loma Linda University in Loma Linda, California.

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Nold, C., Stone, J., O’Hara, K. et al. Block of Granulocyte-Macrophage Colony-Stimulating Factor Prevents Inflammation-Induced Preterm Birth in a Mouse Model for Parturition. Reprod. Sci. 26, 551–559 (2019). https://doi.org/10.1177/1933719118804420

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  • DOI: https://doi.org/10.1177/1933719118804420

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