Abstract
ObjectiveTo compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection.MethodsFetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E2 (PGE2) was measured by enzyme immunoassay.ResultsSubclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE2 was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages.ConclusionsAlmost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.
Highlights
Preterm birth is an important perinatal health problem worldwide
Bacteria proliferate in the lower genital tract and may ascend to the intrauterine cavity [5], where they can trigger an inflammatory response in decidual cells, resulting in secretion of pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and prostaglandins [6,7]
We compared the inflammatory response elicited by primary cultures of decidual cells isolated from cases with preterm labor (PTL) and subclinical intrauterine infection to cases with PTL and no infection to determine if they could be differentiated by their inflammatory response
Summary
Preterm birth is an important perinatal health problem worldwide. The number of preterm births is approximately 12.9 million per year representing 9.6% of births [1]. Intrauterine bacterial infections are considered an important cause of preterm birth [3], and may cause devastating neonatal consequences, such as cerebral palsy [4]. Bacteria proliferate in the lower genital tract and may ascend to the intrauterine cavity [5], where they can trigger an inflammatory response in decidual cells, resulting in secretion of pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and prostaglandins [6,7]. Most of these types of infections are subclinical in nature and cannot be detected without amniotic fluid analysis [5,8]. Evidence to support a role of subclinical intrauterine infection during preterm birth includes the presence of histological chorioamnionitis, clinical infection after preterm birth, positive amniotic fluid cultures, association of lower genital tract microorganisms with preterm birth, and biochemical markers of infection [9]
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