Amniotic fluid adhesion molecules during parturition at term.

AIMS: During term parturition a constant elevation of intercellular adhesion molecule (ICAM-1) as well as increases of endothelial leukocyte adhesion molecule (ELAM-1) and vascular cell adhesion molecule (VCAM-1) in the lower uterine segment and of ICAM-1 in fetal membranes were observed. We examined ELAM-1, ICAM-1 and VCAM-1 during normal term parturition to find out whether amniotic fluid adhesion molecules change accordingly. METHODS: Amniotic fluid specimens of 35 patients undergoing cesarean section at term with various stages of cervical dilatation (<2 cm, n=11; 2-<4 cm, n=10; 4-6 cm, n=6; >6 cm, n=8) and different durations of labor (0 h, n=11; >0 h, n=24) were examined for ELAM-1, ICAM-1 and VCAM-1 by enzyme immunoassay. For statistical analysis one-way ANOVA (cervical dilatation) and unpaired t-test (duration of labor) were used (P<0.05). RESULTS: Neither ELAM-1 nor VCAM-1 correlated with cervical dilatation or with the duration of labor. ICAM-1 showed a tendency to decline with the last phase of cervical dilatation (P=0.06) and a significant decline with labor (P=0.046). CONCLUSIONS: In contrast to adhesion molecules in the lower uterine segment amniotic fluid adhesion molecules ELAM-1 and VCAM-1 do not rise significantly during parturition. The decline of ICAM-1 may be due to a transfer to other compartments (i.e., lower uterine segment or retroplacental blood) thereby contributing to labor and cervical dilatation.

The Role of RCAS1 and oxytocinase in immune tolerance during pregnancy.

OBJECTIVES: To determine and compare the level of RCAS1 (receptor-binding cancer antigen expressed in SiSo cells) in placentas at term as well as oxytocinase/cystine amino peptidase (CAP) serum level a few days before labor in order to evaluate their possible role in the regulation of maternal immune response during pregnancy and in initiation of labor. METHODS: We estimated the RCAS1 content in 44 placental tissue samples, using Western blot method. We also assessed CAP serum level by its enzymatic activity, using L-cystine-di-beta-naphthylamide as a synthetic substrate. The statistical analysis was performed using Shapiro-Wilk procedure. Student's t test was applied to compare the differences between parametric data. A value of p < 0.05 was considered significant. RESULTS: RCAS1 was found in all placental tissue samples examined. The differences in the RCAS1 relative amount depended on the onset of labor, with the highest level in induced labor and the lowest in spontaneous labor. The differences were also observed in the CAP serum level with the highest level in pregnant women whose labor was induced. CONCLUSIONS: We have observed a link between the expression of the two proteins examined and the onset of the labor. Therefore, we posit that RCAS1 and CAP may play a role in the downregulation of the maternal immune response during pregnancy and may participate in the initiation of the labor.

Macrophages and not granulocytes are involved in cervical ripening.

To clarify the role of leucocytes in human cervical ripening and dilatation, cervical biopsies were obtained from six non-pregnant women, eight women undergoing early termination of pregnancy, 18 pregnant women undergoing elective Caesarean section at term (both with and without a ripe cervix as determined by Bishop score) and 11 women after term vaginal delivery. Leucocytes were localised by immunohistochemistry labelling and quantified in subepithelial and deep stromal areas. CD45+ leucocytes were more numerous in the subepithelial area of the cervix than in the deep stroma in all groups (P<0.01). CD14+ macrophages and CD15+ granulocytes were increased in both the subepithelial and deep stromal areas only in the vaginal delivery group (P<0.01). The number of macrophages in the ripening cervix (Bishop score above 4) was higher than in the unripe cervix (Bishop score 4 or less; P<0.05) with no differences in other leucocyte populations. CD3+ CD8+ T cells in the subepithelial area were reduced in late pregnancy and after vaginal delivery (P<0.01), but showed no relationship to Bishop score. Macrophages and granulocytes may be involved in the process of cervical dilatation, but macrophage infiltration into the ripening cervix before labour suggests their role in the ripening process. Reduced numbers of CD3+ CD8+ T-lymphocytes in late pregnancy and after vaginal delivery suggests that local immunity is down-regulated in the late pregnancy period. Regional differences in leucocyte subpopulations in the cervix indicate that leucocyte infiltration is likely to be regulated by local factors.

Interleukin-8 is involved in cervical dilatation but not in prelabour cervical ripening.

Our aim was to determine the amount and source of interleukin (IL)-8 and to study IL-8 receptor expression in the human cervix during pregnancy and after labour. Cervical biopsies were obtained from six non-pregnant women, eight women undergoing pregnancy termination, 17 women undergoing elective caesarean section and 11 women after vaginal delivery. IL-8 levels were compared in women with and without a ripe cervix, as determined by cervical Bishop score and cervicovaginal fetal fibronectin levels. Levels of IL-8 and IL-1beta, a regulator of IL-8 expression, were determined by enzyme-linked immunosorbent assay (ELISA). IL-8, IL-1beta and IL-8 receptor proteins were localized by immunohistochemistry. Compared with late pregnancy, IL-8 levels increased after labour and vaginal delivery (P < 0.01) but there was no correlation with cervical ripening. IL-8 was localized to stromal cells, macrophages and granulocytes. There were no significant differences in IL-1beta levels between groups. IL-8 receptors were expressed primarily on granulocytes and macrophages after vaginal delivery. We conclude that IL-8 is involved in cervical dilatation but not in cervical ripening.

Inflammatory cytokines in newborn infants.

Serum levels of IL-1beta, IL-6 and TNF-alpha were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. MS infinity IL-1beta and IL-6, but not MS infinity TNF-alpha, were significantly higher than those of controls (P<0.0001). IL-1beta values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1beta, IL-6 and TNF-alpha during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.