Cytokine abundance in placental tissues: Evidence of inflammatory activation in gestational membranes with term and preterm parturition,☆☆,

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Abstract

Objectives: This study of the changes in cytokine concentrations in gestational tissues from women with term and preterm labor was undertaken to assess the extent of inflammatory activation associated with spontaneous labor and delivery. Study Design: Extracts of amniotic, chorionic-decidual, and placental tissues from women delivered at term before labor (n = 15), at term after labor (n = 15), and preterm (n = 31) were assayed for interleukin 1β, interleukin 6, and interleukin 8. Results: In amniotic tissues of women delivered by spontaneous labor at term the median interleukin-6, interleukin-8, and interleukin-1β concentrations were 3.8 to 5.4 times those of tissues from women delivered at term without labor (P < .05, Mann-Whitney U test). Interleukin-6 and interleukin-8 concentrations were also significantly increased (3.3-4 times) in chorionic-decidual tissues. Marked increases (approximately 3-6 times) in the concentrations of all 3 cytokines were observed in both amniotic and chorionic-decidual tissues from women with preterm deliveries with respect to those from women with term deliveries after labor. Cytokine concentrations were significantly correlated within amniotic tissues from both women with term delivery after labor and women with preterm delivery and also in preterm chorionic-decidual tissues but not preterm placental tissues. Concentrations of cytokines in the tissues of women delivered preterm were not significantly affected by mode of delivery, treatment with antibiotics, or twin birth. In preterm tissues with evidence of intrauterine infection only amniotic interleukin-1β concentrations were significantly elevated (P < .05). Little or no labor-related change in cytokine concentrations was seen within placental tissues. Conclusions: Increased cytokine abundance in gestational membranes associated with labor supports the view that an inflammatory process is involved in both term and preterm labor. This process does not, however, appear to be evident in the villous placenta. (Am J Obstet Gynecol 1999;181:1530-6.)

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Material and methods

Cytokines and the anticytokine antisera were obtained from R&D Systems (Minneapolis, Minn). Molecular Probes, Inc (Eugene, Ore), supplied 4-methylumbelliferyl phosphate. Pepstatin-A, phenylmethylsulfonylfluoride, and bicinchoninic acid were supplied by Sigma (St Louis, Mo). Bovine serum albumin free of fatty acids and protease inhibitors were supplied by SERVA Electrophoresis GmbH (Heidelberg, Germany).

Results

The gestational age at delivery for both term groups (term no labor and term spontaneous labor) ranged from 37 to 42 weeks. All women had singleton pregnancies, with the exception of 1 twin birth in the term no labor group. There was no clinical evidence of intrauterine infection in any woman in either term group. In the preterm delivery group 65% of the women (20/31) were delivered vaginally. Of the remainder 10 underwent emergency cesarean delivery in labor (duration of labor, 2-84 hours) and

Comment

This is the first comprehensive study of cytokine concentrations in gestational tissues from women delivered at term and preterm with and without labor. The results demonstrate increased levels of inflammatory cytokines in the gestational membranes of women with term or preterm labor. These findings support the view of labor as an inflammatory process and are consistent with the findings of increased cytokine production by gestational tissues after labor at term6, 7, 17 and preterm.10, 11, 12

Acknowledgements

We gratefully acknowledge the assistance of the nursing and theater staff at National Women’s Hospital with the collection of the placental tissues and the excellent technical assistance of Ren-Li Zhou. We also thank Dr M. Battin for screening records for neonatal sepsis.

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Supported by the Auckland University Research Committee, New Zealand Lottery Health Grants Board, the Health Research Council of New Zealand, and the Research Centre in Reproductive Medicine.

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Reprint requests: Jeffrey A. Keelan, PhD, Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Private Bag 92019, Auckland, New Zealand.

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