Role of cytokines and other inflammatory mediators

In spite of impressive advances in biochemistry and molecular biology, it has not yet been possible to fit the individual biochemical components of cervical ripening and dilatation to a uniform clinical moiety or to uncover any regulatory mechanisms. The production of interleukin-8 by activated fibroblasts and macrophages plays a key role in cervical ripening, since this cytokine induces chemotaxis, activation, and degranulation of neutrophilic granulocytes with the consequent release of various proteases, including collagenase. In addition, the extravasation of neutrophilic granulocytes is mediated-as in the early stage of an acute inflammatory reaction-by a brief increase in adhesiveness of vascular endothelium. This is known to be modulated by the cytokine-induced increase in the expression of endothelial adhesion molecules. Furthermore, an increase in pro-inflammatory cytokine and proteinase concentrations in preterm delivery seems to occur at earlier stages of cervical dilatation than in term delivery. It is also well known that in patients with chorioamnionitis, the levels of pro-inflammatory cytokines are elevated in amniotic fluid, maternal serum, cervical secretion, placenta, and other compartments of the placento-maternal unit, and are associated with preterm uterine contractions. We have demonstrated for the first time that cytokine concentrations in the lower uterine segment in patients with chorioamnionitis are strongly elevated. We conclude from our data that increased concentrations of pro-inflammatory cytokines may also play a pivotal role in cervical softening and dilatation during chorioamniotic infection. Our data agree with the hypothesis of Liggins who stated nearly 20 years ago that cervical ripening may be an inflammatory reaction, which leads to increased prostaglandin synthesis, preterm labour and finally to preterm delivery.