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

Abstract

Objective To study 1. whether leucocyte infiltration in placenta tissues is associated with elevated umbilical serum levels of inflammatory mediators, and 2. whether leucocyte infiltration in the presence of neonatal disease is associated with additional increase in mediator levels.Setting University hospital.Population Two groups of women with either normal delivery (n= 82) or delivery complicated by prolonged rupture of the membranes, clinical signs of intrauterine infection or preterm labour (n= 139).Methods Umbilical cord blood and placenta tissues were collected after delivery. Placentas were classified as non‐inflamed (i.e. without leucocyte infiltration, n= 74), or as mild (n= 84), or severe chorioamnionitis (n= 63). Mediator levels were compared between groups.Results Severe chorioamnionitis was associated with elevated levels of tumour necrosis factor (TNF)α, interleukin (IL)‐1β, IL‐6, IL‐8, soluble TNF receptor p55 and p75, IL‐1 receptor antagonist (IL‐1RA), and C‐reactive protein compared with non‐inflamed placentas (all P < 0.05). No differences were found between mild chorioamnionitis and placentas without infiltration. In all, 49 babies suffered from various perinatal diseases, such as clinical sepsis, respiratory distress and asphyxia, and 172 were healthy. Severe chorioamnionitis with subsequent neonatal disease (n= 23) had higher levels of all mediators, except IL‐1β and C‐reactive protein, than severe chorioamnionitis without neonatal disease (n= 40, all P < 0.01), but severe chorioamnionitis was also accompanied by a more intense and widely distributed leucocyte infiltration when neonatal disease developed.Conclusion High grade leucocyte infiltration in placenta tissues is associated with elevated levels of TNFα, IL‐1β, IL‐6, IL‐8, p55, p75, IL‐1RA and C‐reactive protein in umbilical serum. The presence of neonatal disease is associated with advanced chorioamnionitis, and highly elevated levels of both pro‐ and anti‐inflammatory mediators in umbilical serum.

Soluble tumor necrosis factor receptor‐I in preterm infants with chorioamnionitis

“…The correlation between increased levels of cytokines, IL-1b, IL-6, IL-8, sTNFR-I and sTNFR-II, and CAM has been reported in many studies. [1][2][3][4][5][6][7] In the present study, sTNFR-I was significantly increased in severe CAM. Recent investigations have demonstrated that CAM or intrauterine inflammation (or both) may be associated with a pulmonary inflammatory response that plays an important role in the development of CLD.…”

“…Various inflammatory cytokines (interleukin [IL]-1b, IL-6, IL-8) in umbilical cord blood have been reported in infants born to mothers with chorioamnionitis (CAM). [1][2][3][4][5] Gomez et al proposed that a fetal systemic inflammatory response syndrome (FIRS) determined by inflammatory cytokine elevation (IL-6 >11 pg/mL) in fetal blood is a risk factor for severe neonatal morbidity (i.e. sepsis, bronchopulmonary dysplasia, periventricular leukomalacia).…”

Intrapregnancy Non‐Surgical Periodontal Treatment and Pregnancy Outcome: A Randomized Controlled Trial

“…However, comparisons to data obtained from investigation of non-periodontal factors and cord cytokine levels revealed a slightly higher median IL-6 level in POPET study participants when compared with those of a Norwegian-based study of females with histologic chorioamnionitis. 42 This was also the finding for median levels of IL-8 and IL-1b when compared with the findings of a Spanish-based investigation of cord serum cytokines as potential predictors of neonatal sepsis. 43 Bearing in mind the findings of the current POPET study, it is possible that intrapregnancy periodontal treatment may be an ineffective intervention when attempting to target an already pregnancy-activated inflammatory cascade.…”

Neutrophil extracellular traps in acute chorioamnionitis: A mechanism of host defense

“…5,6 In both spontaneous preterm and term labor, this placental lesion is associated with elevated concentrations of pro-inflammatory cytokines such as IL-1α, IL-1β, TNFα, IL-8, and IL-6 in the amniotic fluid [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and umbilical cord blood. [27][28][29][30][31][32][33] Elevated concentrations of these cytokines are linked to adverse neonatal outcomes. 20,21,27,[34][35][36][37][38][39][40][41][42][43][44][45] Therefore, the study herein focused on the mechanisms implicated in acute chorioamnionitis.…”