Zhou Jie, An Xing, Xia Xiuwen, Xiao Wei, Dou Ding, Li Weihong, Huang Qingsong
Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Eur J Med Res. 2025 Jul 2;30(1):542. doi: 10.1186/s40001-025-02755-5.
Idiopathic pulmonary fibrosis (IPF) is an unexplained interstitial lung disease in which senescence is a central risk factor. Senescent cells drive chronic inflammation and fibrosis by the secreting senescence-associated secretory phenotype (SASP). Interleukin-11 (IL-11), a core factor in the SASP, is significantly upregulated in IPF lung tissues.IL-11 promotes lung cellular senescence and chronic inflammation through the activation of the JAK2/STAT3 and MEK/ERK1/2 pathways. It also leads to extracellular matrix protein deposition by promoting fibroblast-myofibroblast transformation, epithelial mesenchymal transition and endothelial mesenchymal transition. Targeting IL-11 has antiaging and fibrotic effects. Nanoparticle delivery therapeutic regimens targeting IL-11 show potential in animal models of IPF, but evidence for their clinical application is lacking. Future studies should focus on the dynamic molecular regulatory mechanisms of IL-11 in IPF, as well as the development of targeted delivery systems and multitarget combined intervention therapeutic regimens. This review systematically analyzes the molecular mechanisms of IL-11 in IPF and provides new perspectives for the treatment of aging-associated pulmonary fibrosis.
特发性肺纤维化（IPF）是一种病因不明的间质性肺疾病，其中细胞衰老为核心危险因素。衰老细胞通过分泌衰老相关分泌表型（SASP）驱动慢性炎症和纤维化。白细胞介素11（IL-11）作为SASP中的一个核心因子，在IPF肺组织中显著上调。IL-11通过激活JAK2/STAT3和MEK/ERK1/2信号通路促进肺细胞衰老和慢性炎症。它还通过促进成纤维细胞-肌成纤维细胞转化、上皮-间质转化和内皮-间质转化导致细胞外基质蛋白沉积。靶向IL-11具有抗衰老和抗纤维化作用。靶向IL-11的纳米颗粒递送治疗方案在IPF动物模型中显示出潜力，但缺乏其临床应用的证据。未来的研究应聚焦于IL-11在IPF中的动态分子调控机制，以及靶向递送系统和多靶点联合干预治疗方案的开发。本综述系统分析了IL-11在IPF中的分子机制，并为衰老相关肺纤维化的治疗提供了新的视角。
