Inflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation

Problem: The inflammasome is implicated in the mechanisms that lead to spontaneous preterm labor (PTL). However, whether there is inflammasome activation in the amniotic cavity of women with PTL and intra-amniotic infection (IAI) or sterile intra-amniotic inflammation (SIAI) is unknown. Method of study: Amniotic fluid samples were collected from women with PTL who delivered at term (n = 31) or preterm without IAI or SIAI (n = 35), with SIAI (n = 27), or with IAI (n = 17). As a readout of inflammasome activation, extracellular ASC (apoptosis-associated speck-like protein containing a CARD) was measured in amniotic fluid by ELISA and the expression of ASC, caspase-1, and interleukin (IL)-1 beta was detected in the chorioamniotic membranes by multiplex immunofluorescence. Acute inflammatory responses in amniotic fluid and the placenta were also evaluated. Results: (a) Amniotic fluid concentrations of ASC and IL-6 were higher in women with PTL and IAI or SIAI than in those who delivered preterm or at term without intra-amniotic inflammation; (b) amniotic fluid concentrations of ASC and IL-6 were lower in women with PTL and SIAI than in those with IAI; (c) there was a significant nonlinear correlation between ASC and IL-6 amniotic fluid concentrations; (d) the expression of inflammasome-related proteins (ASC, caspase-1, and IL-1 beta) in the chorioamniotic membranes was increased in women with PTL and IAI or SIAI than in those who delivered preterm or at term without intra-amniotic inflammation; (e) inflammasome activation in the chorioamniotic membranes was weaker in women with PTL and SIAI than in those with IAI; (f) women with PTL and IAI had elevated amniotic fluid white blood cell counts compared to those without this clinical condition; and (g) severe acute placental inflammatory lesions were observed in women with PTL and IAI and in a subset of women with PTL and SIAI. Conclusion: Inflammasome activation occurs in the settings of intra-amniotic infection and sterile intra-amniotic inflammation during spontaneous preterm labor.