Interleukin-6 Expression in Cord Blood of Patients with Clinical Chorioamnionitis

Abstract

The objective of this study was to define whether IL-6 is an early marker of infection in the newborn. To correlate the occurrence of clinical chorioamnionitis with the levels of IL-6 expression in neonates, IL-6 was measured in cord plasma by ELISA and in mononuclear cells by reverse transcriptase-PCR before and after mitogenic stimulation. Eight neonates were included in each of the following four groups: elective cesarean section, uncomplicated normal spontaneous vaginal delivery, delivery after prolonged rupture of amniotic membranes with no evidence of chorioamnionitis, and delivery with evidence of chorioamnionitis. All 32 neonates were clinically well after delivery, and all 16 babies with prolonged rupture of membranes or clinical chorioamnionitis had negative blood cultures. Elevated IL-6 levels were found only in neonates born to mothers with chorioamnionitis (119.7 +/- 33.5 pg/mL versus 2.71 +/- 0.59 pg/mL, p < 0.005). Mononuclear cells from five of these neonates expressed no IL-6 mRNA in vivo despite elevated levels of IL-6 in their cord plasma. Cord blood mononuclear cells from healthy term babies were capable of synthesizing IL-6 in vitro in response to stimulation with bacterial lipopolysaccharide. These results suggest that IL-6 levels in cord plasma increased with clinical chorioamnionitis, despite the lack of evidence of infection in the neonates. Therefore, we conclude that, although a high level of IL-6 may be a good marker of chorioamnionitis, it may not be a specific marker of infection in the newborn.

Histologic chorioamnionitis and umbilical serum levels of pro‐inflammatory cytokines and cytokine inhibitors

“…In the absence of neonatal disease, we found that chorioamnionitis was less marked, but still associated with elevated levels of mainly pro-inflammatory cytokines (IL-1b, IL-6, IL-8 and IL-1RA). Singh et al 23 have also reported that clinical chorioamnionitis was associated with elevated IL-6 levels in umbilical serum, even in the absence of neonatal disease. These investigators found that cord blood cells were an unlikely source of IL-6, when the neonates were clinically unaffected 23 .…”

“…These investigators found that cord blood cells were an unlikely source of IL-6, when the neonates were clinically unaffected 23 . Although it is unclear whether cytokines may cross from placenta during inflammation, our findings, and the findings reported by Singh et al 23 suggest that inflamed placenta tissues could also be a source of cytokines in the fetal circulation.…”

“…In the feto-placental compartments, cytokines can be secreted from a wide range of cells, including local cells in decidua and chorion, infiltrating macrophages, as well as fetal blood cells 19 -22 . Thus, there are indications that elevated cytokine levels in umbilical serum may reflect placental inflammation 23 , but also a fetal inflammatory response 24 . The purpose of this study was to investigate whether leucocyte infiltration in placenta tissues is associated with elevated levels of TNFa, IL-1b, IL-6, IL-8, p55, p75, IL-1RA and C-reactive protein in umbilical serum, and to investigate whether leucocyte infiltration in the presence of neonatal disease is associated with additional increase in mediator levels.…”

Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis

“…As a rule, early-onset sepsis results from an ascending infection of bacteria from the maternal rectovaginal flora invading the amnion fluid and coming into contact primarily with mucosal cells of the fetal gastrointestinal and respiratory tract. During the last years, several clinical studies, including our own, have demonstrated that levels of proinflammatory cytokines, such as TNF-␣, IL-1␤, IL-6, and IL-8, in plasma are highly elevated in cord blood of neonates with early-onset sepsis (3,4,18,19,27). In the present study, which advantageously could be based upon data on the expression of a variety of cytokines, we were able to show that levels of LBP and sCD14 in plasma also are increased during neonatal early-onset sepsis.…”

Early Markers of Brain Damage in Premature Low-Birth-Weight Neonates Who Suffered from Perinatal Asphyxia and/or Infection

“…7.10), very low Apgar scores and the need for resuscitation with ventilation for 1 3 min [18,21]. In order to define a newborn as having perinatal infection, maternal risk factors were taken into consideration, such as prolonged rupture of membranes or chorioamnionitis [22,23]. In addition, infected newborns were diagnosed as having either proven septicaemia (with positive blood cultures) or suspected septicaemia (with at least 3 clinical and 3 laboratory relevant findings).…”