673: Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) antibody prevents inflammation-induced preterm birth and effects on cervix remodeling using a mouse model

Abstract

The convergence of a multitude of factors promotes inflammation in the reproductive tract as part of a final common pathway leading to preterm birth. Granulocyte macrophage colony stimulating factor (GM-CSF), a pro-inflammatory cytokine, stimulates stem cells to produce monocytes leading to an increase in macrophages, which have been shown to increase in the cervix prior to preterm birth. Previously, our laboratory has shown GM-CSF is upregulated in the cervix and uterus in a mouse model for preterm birth. Therefore, we hypothesized an antibody to GM-CSF will prevent preterm birth by quelling the inflammatory response. Pregnant CD-1 mice on gestational day 17 received either an intrauterine injection of saline or lipopolysaccharide (LPS). Additionally, mice receiving LPS also received an intravenous injection of either anti-mouse GM-CSF or a nonspecific control IgG. After 6 hours, the animals were evaluated for preterm birth and cervices were harvested and processed to assess the density of cell nuclei and resident mature F4/80 macrophages as previously described. Mice treated with LPS + control IgG had a preterm birth rate of 66.7% (started to deliver) compared to a 25% preterm birth rate for mice treated with LPS + anti-mouse GM-CSF (p<0.05 chi square). Moreover, LPS treatment alone reduced cell nuclei density in the cervix, an effect blocked by the anti-mouse GM-CSF antibody treatment. This suggests the LPS-induced cervical remodeling was prevented by GM-CSF blockade due to a reduced presence of macrophages in the LPS + anti-mouse GM-CSF vs LPS only group. These studies demonstrate an antibody to GM-CSF prevents preterm birth through a mechanism that includes effects on cervix remodeling. Further research is needed to determine if antibodies to GM-CSF can be utilized as a therapeutic agent to prevent preterm birth.