Elevated inflammatory mediators from the maternal-fetal interface to fetal circulation during labor. (December 2021) - Huang, Qian
Highlights: Inflammatory mediators up regulated in maternal-fetal interface during labor. Maternal-fetal interface should also include the uterine and fetal circulation. Elevated maternal inflammatory factors could enter the fetal circulation during labor. Abstract: Background: Elevated cytokines, like IL-1βand IL-6, are known to contribute to the pathogenesis of labor. However, the change of inflammatory mediators in maternal-fetal interface to fetal circulation is obscure. Study design and methods: We investigated the changes of inflammatory cytokines, chemokines and macrophage in maternal-fetal interface tissues and fetal circulation of women in labor vs. non-labor. Human myometrium, placenta, decidua, fetal membrane and umbilical blood were obtained from in-labor and non-in-labor women who eventually delivered live, singleton infants at term (>37 weeks gestation) by elective caesarean section. Luminex was used to measure the level of cytokines (TNF-α, IL-1β, IL-6, IL-8) and chemokines (MCP-1, GM-CSF, MIP-1α, MIP-1β) in each sample (tissue and umbilical blood). Macrophage infiltration was demonstrated by immunohistochemistry. Results: During labor, the level of cytokines TNF-α, IL-1β, IL-6 and IL-8 and chemokine MCP-1 and MIP-1β in myometrium is significantly higher (p < 0.05), than those obtained from non-laboring patients. This increase coincides with the influx of macrophage into the myometrium. In addition, IL-1β and IL-8 (p < 0.05) are also up regulated in fetal membrane during labor compared to non-labor. The cytokines do not change significantly in placenta and decidua tissue. In fetal circulation, IL-6 (p < 0.05) is up regulated in umbilical vein blood in labor group. IL-8 (p = 0.08) in umbilical vein also show an increasing trend during labor. Conclusions: There are markedly elevated inflammatory mediators in maternal-fetal interface during labor. The increased maternal inflammatory factors released into the fetal circulation through placenta circulation at the time of labor. This increase coincides with the influx of macrophage into the pregnancy tissue, suggesting that the inflammatory response might play an important role in the onset of labor.