Cytokine Signaling Pathways and Interactions
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Interleukin-11 regulation and signaling in liver disease is summarized; its roles in liver injury, fibrosis, and hepatocellular carcinoma are discussed; its roles in therapeutic strategies targeting the IL-11/IL-11RA axis are discussed; and the opportunities and challenges of IL-11-targeted therapy are evaluated.
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The liver has a remarkable regenerative capacity, but persistent injury caused by drugs, metabolic dysfunction, alcohol, and chronic inflammation can overwhelm this process and promote fibrosis and hepatocellular carcinoma. Interleukin-11 (IL-11), a cytokine that signals through glycoprotein 130 (gp130), was historically considered hepatoprotective; however, accumulating experimental evidence predominantly identifies endogenous IL-11 as an amplifier of liver injury and maladaptive repair. In hepatocytes, IL-11 promotes oxidative stress, mitochondrial dysfunction, and cell death while limiting effective regeneration. In hepatic stellate cells, it sustains myofibroblastic activation and extracellular matrix production, while crosstalk with hepatocytes, macrophages, and the matrix reinforces a fibroinflammatory niche. In hepatocellular carcinoma, experimental and associative clinical evidence implicates IL-11 in tumor growth, invasion, metastatic colonization, postoperative recurrence, stromal remodeling, and immune suppression. These findings have supported the development of therapeutic strategies targeting the IL-11/IL-11RA axis, with the potential to provide broad therapeutic benefits across a wide spectrum of liver diseases. This review summarizes IL-11 regulation and signaling in liver disease; discusses its roles in liver injury, fibrosis, and hepatocellular carcinoma; and evaluates the opportunities and challenges of IL-11-targeted therapy.
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@article{Chen2026Interleukin,
title = {Interleukin-11 Signaling in Liver Disease: Mechanisms, Cellular Crosstalk, and Therapeutic Potential},
author = {Zhiyuan Chen and Yu Fan and Yanhua Qiu and Jun Lin and Meilian Yu and Jinwei Yan and Xianzhi Liu},
journal = {Biomolecules},
year = {2026},
doi = {10.3390/biom16091309},
url = {https://doi.org/10.3390/biom16091309}
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