Harrington Brinley, Thomas Tilu Jain, Tatiparthy Madhuri, Kumar Awanit, Richardson Lauren, Menon Ramkumar, Kammala Ananth Kumar
Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, TX, USA.
Extracell Vesicle. 2025 Jun;5. doi: 10.1016/j.vesic.2025.100066. Epub 2025 Jan 24.
This study investigates the potential of extracellular vesicles (EVs) loaded with interleukin-10 (IL-10) to reduce infection-induced preterm birth (PTB). IL-10 has shown promise in reducing PTB by dampening inflammatory responses, but challenges exist with intraamniotic administration. The study evaluates IL-10 gene-transfected cell-produced EVs containing IL-10 (tIL-10), comparing them with recombinant IL-10 (rIL-10) and rIL-10 incorporated in EVs via electroporation (eIL-10). Characterization of tIL-10 includes size, shape, and molecular markers. Functional assays demonstrate tIL-10's ability to reduce pro-inflammatory cytokine production and extend half-life, with biodistribution in maternal and fetal tissues. The study findings indicate that tIL-10 displays an average size of 108.7 ± 20.5 nm, round with a diameter of ~0.12 μm, and expresses EV markers CD9 and CD81, containing IL-10 cargo. In vitro, LPS stimulation demonstrates that tIL-10 significantly reduces the production of pro-inflammatory cytokines IL-6 and IL-8 from maternal decidual cells. Biodistribution studies reveal tIL-10 presence in placental and fetal membranes within 5 min, persisting for up to 3 h. Pharmacokinetic studies using non-compartmental analysis of plasma data, and the linear trapezoidal method establish key pharmacologic parameters for each drug. Pharmacological findings establish eIL-10 and tIL-10's ability to significantly delay PTB onset after E. coli exposure. These findings underscore the potential of tIL-10 as an effective therapeutic agent for PTB, with implications for clinical practice and further research in reproductive pharmacology.
本研究调查了负载白细胞介素-10（IL-10）的细胞外囊泡（EVs）减少感染诱导的早产（PTB）的潜力。IL-10已显示出通过抑制炎症反应来减少PTB的前景，但羊膜腔内给药存在挑战。该研究评估了含有IL-10的IL-10基因转染细胞产生的EVs（tIL-10），并将其与重组IL-10（rIL-10）以及通过电穿孔法掺入EVs的rIL-10（eIL-10）进行比较。tIL-10的特征包括大小、形状和分子标记。功能测定表明tIL-10具有减少促炎细胞因子产生和延长半衰期的能力，以及在母体和胎儿组织中的生物分布。研究结果表明，tIL-10的平均大小为108.7±20.5nm，呈圆形，直径约为0.12μm，表达EV标记物CD9和CD81，且含有IL-10。在体外，脂多糖刺激表明tIL-10可显著降低母体蜕膜细胞中促炎细胞因子IL-6和IL-8的产生。生物分布研究显示，tIL-10在5分钟内出现在胎盘和胎膜中，并持续长达3小时。使用血浆数据的非房室分析和线性梯形法进行的药代动力学研究确定了每种药物的关键药理学参数。药理学研究结果证实了eIL-10和tIL-10在大肠杆菌暴露后显著延迟PTB发作的能力。这些发现强调了tIL-10作为PTB有效治疗剂的潜力，对临床实践和生殖药理学的进一步研究具有重要意义。
