The immune system during pregnancy undergoes substantial changes to reinforce tolerance of the semi-allogenic foetus until term labour, but disruptions in the immunological balance between innate and adaptive populations can lead to adverse pregnancy outcomes. At present, there are no immunological profiles which can be associated with any aetiology of preterm labour making its prediction difficult. Progesterone is currently being used as a preventative treatment for preterm birth and has been shown to be an effective immune modulator and suppresses inflammation. In myometrial tissue, aminophylline has been shown to enhance the anti-inflammatory effect of progesterone. This project determined cross sectional alterations in systemic and local immune cell phenotypes of women presenting with threatened preterm labour who experienced preterm birth in comparison with term birth pregnancy and secondly, the longitudinal changes in high-risk pregnant women receiving a combination of aminophylline and progesterone intended to prevent preterm labour.
Pregnant participants were recruited at Chelsea and Westminster Hospital, maternal blood and cervical mucus were collected at each visit, and leukocytes were extracted for phenotypic and functional analysis using flow cytometry. Functional assays including: LPS-stimulation
and intracellular cytokine staining were performed later on frozen cells. A cross-Sectional comparison in innate and adaptive cell populations demonstrated that systemic non-classical monocyte and cytotoxic natural killer cell frequencies were lower in women who experienced preterm labour, furthermore, CD4+ TERMA cell frequency was also lower implying that a dysfunction in innate immunity during pregnancy may suppress an adequate adaptive immune response to upcoming antigen exposure. Longitudinal comparison showed that lower non-classical monocyte frequency and markers of natural killer cell maturity were observed in women treated with aminophylline and progesterone supplementation. Whereas, HLA-DR activation on non-classical monocytes was decreased in women treated with progesterone only. Also, LPS-induced monocytes showed no decrease in IL-8, TNF-α and IL-10 secretion in either treatment group. This suggests that aminophylline may have an antagonistic effect to progesterone rather than enhance it, as shown by reduced proportions of non-classical monocytes and decreased cytotoxic potential of an NK cell subset.