Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix

Susanne Abelin Törnblom,Gunvor Ekman-Ordeberg,Birgitta Byström,Aurelija Klimaviciute,Milan Chromek,Annelie Brauner

doi:10.1186/1477-7827-3-39

Abstract

BackgroundHuman cervical ripening is an inflammatory process. In labour at term the mRNA-levels and protein concentrations for interleukin-6 (IL-6) and IL-8 in cervix significantly increase. The aim of this study was to investigate if there are differences in the inflammatory process of preterm and term cervical ripening.MethodsCervical biopsies from 50 singleton pregnant women without clinical signs of infection were allocated to four groups: preterm labour, term labour, preterm not in labour and term not in labour. The protein levels of IL-8, IL-6, monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal t cells expressed and secreted (RANTES) and tumour necrosis factor-alpha (TNF-alpha) were quantified in tissue homogenates by ELISA or Immulite. The mRNA expression of IL-8, MCP-1 and RANTES was studied using RT-PCR. White blood cell count (WBC) and C-reactive protein (CRP) in the blood were determined. For determination of statistically significant differences between study groups Mann-Whitney U test or Kruskal-Wallis test were applied.ResultsProtein concentrations of IL-8, IL-6, and MCP-1 were significantly increased during labour compared to non-labouring groups, whereas no changes were observed for RANTES and TNF-alpha. The mRNA levels of representative cytokines such as IL-8 and MCP-1 increased significantly during labour whereas RANTES mRNA expression remained unchanged. WBC and CRP were significantly higher in the labouring groups as compared to groups not in labour. For neither of the analysed cytokines, WBC or CRP levels were there any changes between preterm and term respective groups.ConclusionOur findings indicate that non-infected preterm cervical ripening is an inflammatory process, just as cervical ripening at term, with cytokines as important mediators.

Highlights

Human cervical ripening is an inflammatory process
The number of patients analysed in each group is marked in each bar in the bar chart
The box represents median value with 25%–75% of all data falling within the box

Summary

Introduction

Human cervical ripening is an inflammatory process. In labour at term the mRNAlevels and protein concentrations for interleukin-6 (IL-6) and IL-8 in cervix significantly increase. The basic mechanisms underlying the initiation of both preterm and term cervical ripening and labour remain largely unknown. Cytokines and several other mediators such as oestrogen, progesterone, nitric oxide and prostaglandins are involved in the human cervical ripening and the remodelling of extracellular matrix [8,9,10,11] This remodelling process can be regarded as an inflammatory reaction [12,13]. The density of immunoactive cells such as leucocytes and macrophages increases 6 to 10-fold at labour compared to first trimester pregnancy [14] They are known producers of a variety of proinflammatory cytokines and matrix metalloproteinase's, and promote the cervical extracellular matrix degradation [13,15,16,17]. Chemokines and cytokines are capable of attracting these immunoactive cells to the site of inflammation and are involved in human pregnancy and parturition [18,19]

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