Increased interleukin-8 levels in cord blood serum of newborn-possible effect of cytokine dysregulation in pregnancies complicated by rheumatic disease on newborn vasculature.

INTRODUCTION

Systemic autoimmune rheumatic diseases (SARDs) are associated with a higher risk of cardiovascular diseases. During pregnancy, maternal immune disbalance might impact the vasculature of the newborn. We, therefore, aimed to investigate a possible association between maternal inflammatory rheumatic disease and inflammatory signaling in the umbilical cord of the newborn.

METHODS

This single-center study included neonates of women with connective tissue disorders (CTDs) and inflammatory joint diseases (IJDs) and healthy controls (HC).

RESULTS

The tissue of umbilical cords (UCs) of neonates born to IJD patients showed elevated ICAM-1 expression, indicating increased inflammatory response. Monocyte subsets in venous umbilical cord blood (VUCB) showed an equal distribution of non-classical monocytes in all groups. Leukocytes in VUCB showed no significant differences between the three groups although a trend of Treg reduction and an increase in cytotoxic T lymphocytes (CTLs) in the IJD offspring group were detectable. Cytokine levels of VUCB serum were overall low, except IL-8 with significantly elevated concentrations in the IJD neonate group. In the maternal serum of IJD patients, IL-8 levels were low comparable to IL-8 in healthy umbilical cord vein (UCV) serum, indicating a de novo synthesis of IL-8 in the UCV of neonates. Platelet-derived growth factor AA (PDGF-AA) was significantly reduced in the sera of IJD and CTD offspring. Furthermore, a significant reduction of human UCV smooth muscle cell (HUVSMC) proliferation incubated with plasma of the VUCB-IJD sera of neonates, possibly an effect of reduced PDGF-AA levels, is detectable.

CONCLUSION

Well-controlled SARD during pregnancy does not seem to influence most of the inflammatory signaling in the UC. However, the elevated levels of IL-8 in the serum of neonates of women with IJD might have an impact on long-term vascular health and cardiovascular events.