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

BACKGROUND: Human 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. METHODS: Cervical 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. RESULTS: Protein 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. CONCLUSION: Our findings indicate that non-infected preterm cervical ripening is an inflammatory process, just as cervical ripening at term, with cytokines as important mediators.

mRNA expression and localization of bNOS, eNOS and iNOS in human cervix at preterm and term labour.

BACKGROUND: Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term. METHODS: The three isomers of NOS--inducible (iNOS), endothelial (eNOS) and neuronal (bNOS)--were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL), term labour (TL), preterm not in labour (PTnotL) and term not in labour (TnotL) patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups. RESULTS: Patients in preterm labour had significantly (p < 0.01) higher mRNA levels of all the three NOS isomers compared to those in term labour. Women not in labour, irrespective of gestational age, thus with unripe cervices, had significantly lower eNOS mRNA levels compared to those in labour (p < 0.01). Immunoreactivity for all three NO synthases was observed in each examined sample in all groups. The bNOS staining was the most prominent. CONCLUSION: The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.

15-hydroxyprostaglandin dehydrogenase and cyclooxygenase 2 messenger ribonucleic acid expression and immunohistochemical localization in human cervical tissue during term and preterm labor.

Here we have examined the enzymes cyclooxygenase (COX)-2 and 15-hydroxyprostaglandin dehydrogenase (15-OH PGDH) in pregnant human cervix. In biopsies taken transvaginally after preterm and term elective cesarean sections and vaginal deliveries, the levels of mRNA coding for COX-2 and 15-OH PGDH were assessed by Northern blotting. The cellular localization of the COX-2 and 15-OH PGDH proteins was determined by immunohistochemical analysis. COX-2 and 15-OH PGDH mRNAs were expressed at detectable levels in the cervical biopsies from all four groups of subjects. At cesarean sections (unripe cervix), the level of 15-OH PGDH mRNA was significantly higher than the level in the ripe cervix at the time of partus, irrespective of the gestational length. In contrast, the level of COX-2 mRNA was similar in all subjects. Immunoreactivity of COX-2 and 15-OH PGDH was expressed by activated fibroblasts. The present investigation documents the expression and cellular localization of COX-2 and 15-OH PGDH in the preterm and term pregnant human cervix. This observation indicates that both preterm and term cervical ripening is associated with decreased degradation of prostaglandins.