Immune Modulation of Inflammasome Stimulates NLRP3 and IL-1β Expression in Preeclampsia: Insights into the Role of Anti-Inflammatory Agents in Prevention of Low Birth Weight

Abstract

Background: Preeclampsia remains a leading cause of maternal and neonatal morbidity and mortality. It is characterized by altered local and systemic immune regulation and a rise in proinflammatory cytokines. The inflammasome is a cytosolic protein complex that mediates innate immune responses through promoting the secretion of interleukin-1beta (IL-1β). This study aimed to investigate the nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain-containing protein 3, inflammasome activation in preeclampsia (PE), its relation to IL-1β and their association with PE outcomes. Methods: Placenta and blood were collected from 25 control pregnant women and 50 preeclamptic women. Pyrin domain-containing protein 3 (NLRP3) and IL-1β gene expression were quantified by real-time polymerase chain reaction (PCR). Results: Placental and blood relative gene expression levels of NLRP3 and IL-1β were significantly higher in mild and severe PE than in controls. A significantly higher blood expression of NLRP3 was noticed in the low birth weight subgroup compared to the normal birth weight subgroup (p = 0.03) in the severe PE group. Both biomarkers levels in placenta and blood showed significant negative correlations with the weight of newborn. The strong positive correlation (p < 0.0001, r = 0.9) between NLRP3 and IL-1β suggested that IL-1β response mostly depend on NLRP3 inflammasome. Conclusions: These results suggest the presence of excessive activation of NLRP3 and subsequently increased production of active IL-1β that may predispose placental inflammation in severe PE and subsequently, low neonatal birth weight and shortened gestational age.