Inflammatory mediators : their roles during pregnancy and parturition

• Main Author: Denison, Fiona Charlotte
• Published: University of Edinburgh 2000
• Subjects: 618
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649482

The aim of this thesis was to investigate the role of inflammatory mediators, specifically cytokines, prostaglandin E₂ (PGE₂), nitric oxide (NO), metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) during pregnancy and parturition. Part 1. This investigated the roles of inflammatory mediators in the initiation and maintenance of pregnancy. The role of seminal plasma, specifically its component PGs (PGE₂ and 19-hydroxy PG), in the initial adaptation of the maternal immune response to pregnancy was studied in the non-pregnant cervix, peripheral blood and a monocyte cell line. PGs stimulated release of IL-10, thus favouring development of a T-helper (Th)-2 type, pregnancy favourable immune response. They also stimulated release of the neutrophil chemotactic factor IL-8, which may be involved in mediating post-coital cervical leukocytosis. Furthermore, peripheral blood from pregnant women, specifically the mononuclear cell (CD14⁺) fraction, released significantly more monocyte chemotactic peptide-1 (MCP-1), which also favours a Th-2 type immune response, than that from non-pregnant women. Release of IL-8 and RANTES was comparable between groups. the concentrations of MCP-1, IL-8 and RANTES in the fluid compartments within the first trimester uterus were also examined. The chemokines were differentially distributed with MCP-1 and IL-8 being present in amniotic fluid, maternal serum and extra-embryonic coelom with highest levels of both in the latter compartment. RANTES was only detectable in peripheral serum. These findings support the hypothesis that inflammatory mediators are important in the initiation and maintenance of pregnancy and may play a role in early placental and fetal development. Part 2. This examined the involvement and regulation of inflammatory mediators in parturition. Cervical ripening involves tissue remodelling mediated by inflammatory mediators, infiltrating cells, MMPs and TIMPs. However their regulation in the cervix are not well understood.