An extensive remodelling process, referred to as cervical ripening, takes place in the cervical tissue during pregnancy and labour. It is recognized as softening and dilation of the cervical canal, and starts as a slow process during pregnancy, becoming rapid close to partum. In this study we focus on cytokines as possible mediators of this final remodelling. mRNA levels for interleukin (IL)-8, IL-6 and granulocyte colony-stimulating factor (G-CSF) were upregulated in the ripe postpartum cervical tissue (n = 8) compared to the unripe state (n = 9). Likewise, released cytokine concentrations increased from non-pregnant (n = 11) to the term-pregnant group (n = 13) with a further increase at partum (n = 16). IL-8 concentrations increased 4-fold from non-pregnant to term-pregnant (P<0.01), and a further 10-fold to postpartum state (P<0.0001). Concentrations of IL-6 and G-CSF were similarly increased. Specific IL-8 immunostaining was identified in the epithelia of pregnant cervical tissue (n = 7) and was most pronounced in the epithelia and stroma of postpartum tissue (n = 4). In conclusion, IL-8, IL-6 and G-CSF increase in the human cervix during the ripening process, indicating their important role in the cervical remodelling. These data demonstrate that cervical ripening is similar to an inflammatory process.

Increased amount of abdominal fat and obesity are common in polycystic ovary syndrome (PCOS). A higher prevalence of bulimia nervosa and greater cravings for sweets have also been reported in these patients. The present study aimed to compare meal-related appetite and secretion of the 'satiety peptide' cholecystokinin (CCK) and glucose regulatory hormones in PCOS women and controls. Sixteen pairs of women with PCOS and controls matched for age and body mass index participated in the study. After an overnight fast, blood samples were collected during ingestion of a standardized meal. We determined basal and postprandial blood levels of CCK, insulin, C-peptide, glucagon, cortisol, growth hormone and glucose. Self-ratings of appetite were assessed by a visual analog scale. PCOS women had a significantly lower meal-related CCK response (p < 0.05) with no association with satiety, as in the controls (r = 0.64). There was a tendency to higher ratings of craving for sweets in PCOS women (p = 0.07) but no correlation with insulin, as in the controls (r = 0.50). Within the PCOS group, ratings of craving for sweets were inversely related to testosterone (r = - 0.60) and the CCK response was positively correlated with levels of free testosterone (r = 0.50). We conclude that women with PCOS have reduced postprandial CCK secretion and deranged appetite regulation associated with increased levels of testosterone. Impaired CCK secretion may play a role in the greater frequency of binge eating and overweight in women with PCOS.

1Cervical ripening is necessary for successful delivery. As cytokines are believed to be 2 involved in this process, the aim of this study was to investigate possible changes in the 3 mRNA and protein expression of pro-inflammatory (interleukin (IL)-1α, IL-1β, IL-12, IL-18) 4 and anti-inflammatory (IL-4, IL-10, IL-13) cytokines in the human cervix during pregnancy, 5 term and preterm labor. Cervical biopsies were taken from 59 women: 21 at preterm labor, 24 6 at term labor, 10 at term not in labor and 4 from non-pregnant women. mRNA was analyzed 7 with real-time RT-PCR and protein expression and/or secretion with immunohistochemistry 8 and ELISA. There was an upregulation of mRNA for IL-10, IL-13, IL-1α and IL-1β in the 9 laboring groups, while mRNA for IL-12 and IL-18 was downregulated (p<0.05). IL-4 mRNA 10 was detected more frequently, while IL-12 mRNA expression was lower, in the preterm labor 11 group than in the term labor group (p<0.05). The protein levels of IL-4 and IL-12 were lower 12 and IL-18 tended to be higher in the labor groups, while IL-10 protein levels were unaffected 13 by labor. IL-4 protein levels were significantly higher in the preterm subgroup with bacterial 14 infection than in the non-infected group (p<0.05). IL-10 had higher expression in squamous 15 epithelium at preterm labor than at term (p<0.05). In conclusion, the major changes in pro-16 inflammatory and anti-inflammatory cytokine mRNA and protein expression in cervix occur 17 during the labor process irrespective of the length of gestation. However, our results indicate 18 that dysregulation of anti-inflammatory cytokines in the human cervix could be involved in 19 the pathogenesis of preterm labor. 20 21

The results indicate that MMP-8 is involved in the process of cervical ripening, and that MMP-1 and -3 and their inhibitors TIMP-1 and -2 may also play a role in this complicated process.

This study was supported financially by the Swedish Research Council (A.L.H., 20324), Karolinska Institutet and the Stockholm County Council. None of the authors has any conflict of interest to declare.