IL-37 alleviates inflammatory effects and NLRP3 inflammasome activation in LPS-induced preterm birth.

Preterm birth (PTB), a complication affecting 5% to 11.1% of pregnancies worldwide, imposes adverse consequences for both families and society. Previous studies have revealed that interleukin-37(IL-37) is involved in PTB in foetal membranes and that NLRP3 inflammasome activation promotes labour. However, the direct effects of IL-37 on PTB, as well as the underlying mechanisms, remain unclear. Foetal membrane and placental tissues were collected from term and preterm women to evaluate IL-37 expression. Using an LPS-induced mouse model of preterm labour, we assessed the effects of recombinant interleukin-37(rhIL-37) on inflammatory cytokine release and NLRP3 inflammasome activation. Additionally, the underlying mechanism was further investigated using LPS-induced HTR-8/Svneo human trophoblast cells. IL-37 mRNA expression was downregulated in foetal membrane tissues (p < 0.05) and placental tissues(p > 0.05) in preterm patients. rhIL-37 delayed LPS-induced preterm labour in mice for at least 24 h. rhIL-37 inhibited inflammatory cytokine release(IL-1β, IL-6, and TNF-α ), activation of the NF-κB p65, and activation of the NLRP3 inflammasome (NLRP3, caspase-1, and ASC) in both in vivo and in vitro experiments. In addition, the anti-inflammatory effects of rhIL-37 were reversed by treatment with nigericin. IL-37 is downregulated in patients with PTB, and rhIL-37 reduces inflammation and NLRP3 inflammasome activation via the NF-κB/NLRP3 inflammasome axis. Thus, rhIL-37 hold therapeutic potential as a therapeutic approach for the prevention of PTB.