Abstract / Summary
Interleukin 37 (IL‑37), a member of the IL‑1 family, is recognized as an anti‑inflammatory cytokine. The anti‑inflammatory properties of recombinant human (rh)IL‑37 have been confirmed in vitro and its protective effects have been extensively demonstrated in various in vivo models. These include inflammatory disease models treated with rhIL‑37 protein or transfected with plasmids encoding human IL‑37 cDNA, as well as in IL‑37 transgenic mice. IL‑37 exerts its anti‑inflammatory functions through intracellular pathways involving Smad3, and via extracellular signaling through the IL‑18 receptor α chain (IL‑18R)α/IL‑1R8 complex or the IL‑18 binding protein/IL‑18Rβ axis. It maintains immune homeostasis by modulating the expression and activity of transcription factors, cytokines and chemokines, thereby balancing pro‑inflammatory and anti‑inflammatory responses. Beyond suppressing innate and adaptive immune responses, IL‑37 alleviates gynecological conditions, inflammatory disorders and metabolic disturbances associated with polyendocrine metabolic ovarian syndrome, including obesity, insulin resistance and impaired glucose tolerance. Furthermore, IL‑37 significantly inhibits the proliferation, invasion, metastasis and angiogenesis of ectopic endometrial cells and gynecological tumor cells. In recent years, interest in the role of IL‑37 in gynecological and obstetric diseases has increased substantially. Accordingly, this review summarizes recent advances in understanding the involvement of IL‑37 in inflammatory conditions and related tumors in gynecology and obstetrics. Unless otherwise specified, IL‑37 in this article refers to the IL‑37b isoform.