534: Anti-granulocyte macrophage-colony stimulating factor (GM-CSF) antibody prevents the upregulation of cyclooxygenase-2 in a mouse model

Abstract

Preterm birth is believed to be a final common pathway of a multitude of instigating factors, and inflammation plays a critical role in preterm birth. Previous work from our laboratory has shown granulocyte macrophage-colony-stimulating factor (GM-CSF), a pro-inflammatory cytokine, is upregulated in the uterus in a mouse model of preterm birth. We have also shown treatment with an antibody to GM-CSF will prevent preterm birth within six hours. Therefore, we hypothesized treatment with an antibody to GM-CSF will prevent the upregulation of contraction associated proteins in the uterus leading to preterm birth. For this study, we utilized a mouse model of preterm birth. On embryonic day 17, pregnant CD1 mice were anesthetized and received an intrauterine injection of lipopolysaccharide (LPS) along with either an intravenous injection of anti-mouse GM-CSF or control antibody. After six hours the uteri were harvested and analyzed for expression of the oxytocin transmembrane receptor (OXTR), cyclooxygenase-2 (COX-2), or connexin-43 (Cx43) using quantitative polymerase chain reaction (qPCR). LPS increased the expression of COX-2 (p<0.001) compared to mice receiving an intrauterine injection of saline, and treatment with the anti-mouse GM-CSF antibody resulted in a decreased expression of COX-2 (p<0.05). Treatment with LPS did not increase the expression of OXTR or Cx43 compared to control mice, although the GM-CSF antibody did decrease the expression of Cx43 compared to mice treated with the control antibody. These studies demonstrate treatment with the anti-mouse GM-CSF antibody prevents upregulation of the contraction associated protein COX-2 in the uterus utilizing an inflammatory mouse model. Further research is needed to determine if antibodies to GM-CSF can be utilized as a therapeutic agent to prevent preterm birth.