Inflammation in preterm birth: Novel mechanism of preterm birth associated with innate and acquired immunity

Abstract

Preterm birth (PB) is the most-frequent complication occurring during pregnancy, with a significant impact on neonatal morbidity and mortality. Chorioamnionitis (CAM), the neutrophil infiltration into chorioamniotic membranes, is a major cause of PB. However, several cases of PB have also been reported without apparent pathogenic infection or CAM. Such cases are now attributed to “sterile inflammation.” The concept of sterile inflammation has already attracted attention in various diseases, like cardiovascular diseases, diabetes, and autoimmune diseases; recently been discussed for obstetric complications such as miscarriage, PB, gestational hypertension, and gestational diabetes. Sterile inflammation is induced by alarmins, such as high-mobility group box 1 (HMGB1), interleukins (IL-33 and IL-1α), and S100 proteins, that are released by cellular damage without apparent pathogenic infection. These antigens are recognized by pattern-recognition receptors, expressed mainly on antigen-presenting cells of decidua, placenta, amnion, and myometrium, which consequently trigger inflammation. In reproduction, these alarmins are associated with the development of various pregnancy complications, including PB. In this review, we have summarized the development of PB related to acute CAM, chronic CAM, and sterile inflammation as well as proposed a new mechanism for PB that involves innate immunity, acquired immunity, and sterile inflammation.