■綜説
早産と炎症―無菌性炎症を中心とした新たな早産メカニズム―
根岸 靖幸
日本医科大学微生物学免疫学教室
日本医科大学産婦人科学教室
Inflammation in Preterm Birth-The Mechanisms by Which Sterile Inflammation Causes Preterm Birth-
Yasuyuki Negishi
Department of Microbiology and Immunology, Nippon Medical School
Department of Obstetrics and Gynecology, Nippon Medical School
Preterm birth (PB) is a common complication of pregnancy and is associated with neonatal morbidity and mortality. The major cause of PB has long been considered to be the presence of acute chorioamnionitis (aCAM), which is characterized by neutrophil infiltration into the chorioamniotic membranes induced by bacterial infection. However, recent studies have revealed that PB often occurs in the absence of aCAM and bacterial infection. Attention has focused, therefore, on sterile inflammation as a possible cause. Sterile inflammation has been implicated in various conditions, including cancer, diabetic kidney disease, cardiovascular disease, and pulmonary disorders, and it is also suspected to play a role in the pathogenesis of many obstetric complications, such as PB, infertility, recurrent pregnancy loss, and preeclampsia. Sterile inflammation is induced by such endogenous molecules as high mobility group box 1 (HMGB1), IL-1α, IL-33, heat shock protein, and S100 protein, which are released as a result of tissue and cellular damage in the absence of infection. Exogenous particles like nanoparticles, silica, and asbestos also facilitate sterile inflammation. Collectively, these molecules are called alarmins. Recent studies have suggested that alarmins (particularly HMGB1, IL-1α, and cell-free fetal DNA) are closely associated with the occurrence of PB without apparent infection. Moreover, innate immune cells, such as dendritic cells, macrophages, and invariant natural killer T (iNKT) cells, are also considered to be important players in PB caused by sterile inflammation. The immunostimulatory activity of dendritic cells and macrophages in the placenta is enhanced by stimulation with alarmins, and these cells may activate downstream effector cells, iNKT cells, NK cells, neutrophils, and T cells, leading to excessive sterile inflammation and PB. This review focuses on the role of inflammation in PB, and particularly the mechanisms by which sterile inflammation causes PB.
日医大医会誌 2022; 18(2), 194-201
Key words
preterm birth, sterile inflammation, innate immunity, chorioamnionitis, alarmin
Correspondence to
Yasuyuki Negishi, Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
E-mail：negi@nms.ac.jp
受付：2022年2月4日 受理：2022年3月10日 |
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