Interleukin-11: A central integrative hub driving pathological progression from pulmonary inflammation and fibrosis to cancer

Interleukin-11 (IL-11), a member of the IL-6 cytokine family, plays a pivotal role in driving pulmonary inflammation, fibrosis, and cancer progression. As a distinct regulator, IL-11 exerts contrasting effects depending on the disease context. During acute inflammation, IL-11 maintains alveolar integrity, mitigates oxidative stress, and modulates immune responses. However, chronic IL-11 signaling promotes airway remodeling and fibrosis in diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). We propose an ecological model in which IL-11 acts as a "keystone species" within interconnected pulmonary niches-epithelial, stromal, and immune cells-that collectively facilitate the transition from inflammation to fibrosis and ultimately to cancer. Targeted therapeutic strategies against IL-11 signaling are emerging, including neutralizing antibodies, receptor antagonists, engineered decoy ligands, and IL-11Rα-directed fusion toxins. Additionally, RNA interference (RNAi)-based approaches and small-molecule inhibitors targeting downstream IL-11 pathways (e.g., JAK/STAT3, MEK/ERK) have demonstrated substantial preclinical efficacy. This review underscores IL-11's critical role in pulmonary disease pathogenesis and highlights its potential as a therapeutic target. Further clinical validation and biomarker development are essential to translate these insights into personalized treatment strategies for diseases spanning inflammation, fibrosis, and cancer.