Cytokines and infection-induced preterm labour

Abstract

Our present understanding of the physiologic role of prostaglandins during pregnancy and, in particular, the precise function of these agents in the initiation of human parturition, is limited. This uncertain posture persists in spite of evidence (reviewed in detail recently by Challis and Olson 1988) in favour of a fundamental role for prostaglandins in a host of physiological processes in reproductive biology, including the onset and progression of labour. All investigators agree that prostaglandin E2 (PGE2) and prostaglandin F2, (PGF2,) can act, pharmacologically, as uterotonins (to cause myometrial contraction) when administered to pregnant women at any stage of gestation; moreover, the ingestion of inhibitors of prostaglandin synthesis by pregnant women is associated with a delay in the onset of labour-whether spontaneous or induced. There is much evidence in support of the conclusion that there is an increase in the rate of production of prostaglandins during labour: namely, during labour, there are increases in the levels of PGE2, PGF2, and 13,14-dihydro-15-keto-PGF2, (PGFM) in amniotic fluid and increases in PGFM in maternal blood. Also, prostaglandins will effect cervical dilatation. However, it has not been proven that prostaglandins serve as the physiological uterotonins of parturition or that prostaglandins are obligatorily involved in parturition at all stages of pregnancy, i.e. term and preterm labour. The evidence that there is an increase in the levels of prostaglandins in the maternal or fetal compartment prior to the onset of labour is limited. The possibility that the increase in prostaglandins is a consequence of labour (and not an initiating event) has not been excluded. Importantly, based on the findings of studies conducted recently, the possibility exists that labour (and delivery) may occur in some preterm pregnancies in the absence of an increase in prostaglandin production of the same magnitude that occurs during normal labour at term (Cox et al. 1989). Thus, we suggest that it is timely to consider the role of prostaglandins in the parturitional process with a new view, i.e, one that may enable an expansion of our understanding of the biochemical events involved in the initiation of parturition at term and preterm. Nowadays, the statement that human pregnancy is characterized by profound alterations in a host of biochemical and physiologic processes that encompass most all organ systems may rightly be considered timeworn. Yet, recent analyses of this well-recognized premise have led to the concepts that among these pregnancy-altered processes are those that facilitate recognition of pregnancy and, thereby, adaptation to pregnancy and maintenance of pregnancy. Perhaps the most remarkable compliance of normal human pregnancy is the maintenance of uterine quiescence for 38 weeks. For more than 99% of gestation, normal pregnancy is characterized by remarkable uterine repose and equanimity -a state that is essential to the maintenance of pregnancy. This quiescent state is uncommon for this smooth