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Problem: Preterm birth is commonly preceded by preterm labor, a syndrome that is causally linked to both intra‐amniotic infection and intra‐amniotic inflammation. However, the stereotypical cellular immune responses in these two clinical conditions are poorly understood. Method of study: Amniotic fluid samples (n = 26) were collected from women diagnosed with preterm labor and intra‐amniotic infection (amniotic fluid IL‐6 concentrations ≥2.6 ng/mL and culturable microorganisms, n = 10) or intra‐amniotic inflammation (amniotic fluid IL‐6 concentrations ≥2.6 ng/mL without culturable microorganisms, n = 16). Flow cytometry was performed to evaluate the phenotype and number of amniotic fluid leukocytes. Amniotic fluid concentrations of classical pro‐inflammatory cytokines, type 1 and type 2 cytokines, and T‐cell chemokines were determined using immunoassays. Results: Women with spontaneous preterm labor and intra‐amniotic infection had (a) a greater number of total leukocytes, including neutrophils and monocytes/macrophages, in amniotic fluid; (b) a higher number of total T cells and CD4+ T cells, but not CD8+ T cells or B cells, in amniotic fluid; and (c) increased amniotic fluid concentrations of IL‐6, IL‐1β, and IL‐10, compared to those with intra‐amniotic inflammation. However, no differences in amniotic fluid concentrations of T‐cell cytokines and chemokines were observed between these two clinical conditions. Conclusion: The cellular immune responses observed in women with preterm labor and intra‐amniotic infection are more severe than in those with intra‐amniotic inflammation, and neutrophils, monocytes/macrophages, and CD4+ T cells are the main immune cells responding to microorganisms that invade the amniotic cavity. These findings provide insights into the intra‐amniotic immune mechanisms underlying the human syndrome of preterm labor. [ABSTRACT FROM AUTHOR]

Problem: Pyroptosis, inflammatory programmed cell death, is initiated through the inflammasome and relies on the pore‐forming actions of the effector molecule gasdermin D. Herein, we investigated whether gasdermin D is detectable in women with spontaneous preterm labor and sterile intra‐amniotic inflammation or intra‐amniotic infection. Method of study: Amniotic fluid samples (n = 124) from women with spontaneous preterm labor were subdivided into the following groups: (a) those who delivered at term (n = 32); and those who delivered preterm (b) without intra‐amniotic inflammation (n = 41), (c) with sterile intra‐amniotic inflammation (n = 32), or (d) with intra‐amniotic infection (n = 19), based on amniotic fluid IL‐6 concentrations and the microbiological status of amniotic fluid (culture and PCR/ESI‐MS). Gasdermin D concentrations were measured using an ELISA kit. Multiplex immunofluorescence staining was also performed to determine the expression of gasdermin D, caspase‐1, and interleukin‐1β in the chorioamniotic membranes. Flow cytometry was used to detect pyroptosis (active caspase‐1) in decidual cells from women with preterm labor and birth. Results: (a) Gasdermin D was detected in the amniotic fluid and chorioamniotic membranes from women who underwent spontaneous preterm labor/birth with either sterile intra‐amniotic inflammation or intra‐amniotic infection, but was rarely detected in those without intra‐amniotic inflammation. (b) Amniotic fluid concentrations of gasdermin D were higher in women with intra‐amniotic infection than in those with sterile intra‐amniotic inflammation, and its expression in the chorioamniotic membranes was associated with caspase‐1 and IL‐1β (inflammasome mediators). (c) Decidual stromal cells and leukocytes isolated from women with preterm labor and birth are capable of undergoing pyroptosis given their expression of active caspase‐1. Conclusion: Pyroptosis can occur in the context of sterile intra‐amniotic inflammation and intra‐amniotic infection in patients with spontaneous preterm labor and birth [ABSTRACT FROM AUTHOR]