Abstract
The maternal immune response is essential for successful pregnancy, promoting immune tolerance to the fetus while maintaining innate and adaptive immunity. Uncontrolled, increased proinflammatory responses are a contributing factor to the pathogenesis of preeclampsia. The Th1/Th2 cytokine shift theory, characterised by bias production of Th2 anti-inflammatory cytokine midgestation, was frequently used to reflect the maternal immune response in pregnancy. This theory is simplistic as it is based on limited information and does not consider the role of other T cell subsets, Th17 and Tregs. A range of maternal peripheral cytokines have been measured in pregnancy cohorts, albeit the changes in individual cytokine concentrations across gestation is not well summarised. Using available data, this review was aimed at summarising changes in individual maternal serum cytokine concentrations throughout healthy pregnancy and evaluating their association with preeclampsia. We report that TNF-α increases as pregnancy progresses, IL-8 decreases in the second trimester, and IL-4 concentrations remain consistent throughout gestation. Lower second trimester IL-10 concentrations may be an early predictor for developing preeclampsia. Proinflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-8, and IL-6) are significantly elevated in preeclampsia. More research is required to determine the usefulness of using cytokines, particularly IL-10, as early biomarkers of pregnancy health.
Highlights
The importance of the maternal immune system in the establishment and maintenance of successful pregnancy is well researched
We found substantial evidence of changes in cytokine concentrations that occur during healthy pregnancy
It is likely that Tumour necrosis factor (TNF)-α increases as pregnancy progresses, Interleukin TNF (IL)-8 decreases in the second trimester, and IL-4 concentrations remain consistent throughout gestation
Summary
The importance of the maternal immune system in the establishment and maintenance of successful pregnancy is well researched. The maternal immune system must support immune tolerance to the fetus while maintaining innate and adaptive responses to prevent pathogen invasion. Research exploring the maternal-fetal interface dates back to 1953 when Medawar defined the fetus as an allograft [3] and the uterus was originally proposed to be an immune privileged site [4]. Further theories exist on how the maternal immune response adapts to pregnancy and enables survival of the fetus including the proposed anatomical barrier effect between the mother and fetus [5], maternal systemic and local immune suppression, a lack of major histocompatibility complex (MHC) antigens on fetal tissue, and the maternal Th1/Th2 cytokine shift [6]. Research has focused on the maternal cytokine profile and how it differs during pregnancy, suggesting that a balance between pro- and antiinflammatory responses is important for optimal pregnancy outcome [7]
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