Fetuses Delivered Following Preterm Prelabor Rupture of the Membranes are Capable of Stimulating a Proinflammatory Response in Endothelial Cells

Abstract

Preterm premature rupture of the membranes (PROM) has been attributed to ascending infection and a choriodecidual inflammatory response (ie, on the maternal side). However, on the fetal side those most at risk of morbidity have a systemic proinflammatory cytokine response. We have recently defined a similar proinflammatory response in pregnancies complicated by vascular disease on the fetal side of the placenta. A factor(s) present in fetal plasma from these pregnancies can stimulate human umbilical vein endothelial cells (HUVECs) to express mRNA for the proinflammatory cytokines, interleukin (IL)-6 and IL-8. The hypothesis of this study was that a similar factor(s) was present in preterm PROM. A standard culture of HUVECs was incubated with fetal plasma, obtained immediately following delivery, from normal pregnancies delivering vaginally at term (n=16) and pregnancies delivering following preterm PROM (n=19). Expression of mRNA for IL-6 and IL-8 was assessed by reverse transcription polymerase chain reaction (RT-PCR) and standardized to GAPDH mRNA expression. Endothelial cell expression of IL-6 mRNA (median [25-75th centile] 0.295 [0.252-0.507] vs term vaginal delivery 0.208 [0.151-0.307]; P=.009) was enhanced in response to the fetal plasma from PROM cases compared to pregnancies delivering vaginally at term. In contrast, mRNA expression of IL-8 (median [25-75th centile] preterm PROM 0.41 [0.21-0.78] vs term vaginal delivery 0.49 [0.16-0.68]; P=.46) was not different in the two groups. We have demonstrated that in fetuses delivered following preterm PROM there is a factor(s) capable of stimulating a local endothelial cell proinflammatory cytokine (IL-6) response. This factor(s) that we have demonstrated may be responsible for the increased cytokine production seen in fetuses with the fetal inflammatory response syndrome.