IL‐11 in cardiac and renal fibrosis: Late to the party but a central player

Fibrosis is a pathophysiological hallmark of cardiorenal disease. In the heart, fibrosis leads to contractile dysfunction and arrhythmias; in the kidney, it is the final common pathway for many diseases and predicts end‐stage renal failure. Despite this, there are currently no specific anti‐fibrotic...

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Bibliographic Details
Published in:British journal of pharmacology 2020-04, Vol.177 (8), p.1695-1708
Main Authors: Corden, Benjamin, Adami, Eleonora, Sweeney, Mark, Schafer, Sebastian, Cook, Stuart A.
Format: Article
Language:English
Subjects:
Animal models
Animals
Autocrine signalling
Coronary artery disease
Disease
Fibroblasts
Fibroblasts - pathology
Fibrosis
Heart
Heart diseases
Humans
Interleukin 1
Interleukin-11
Interleukin-11 Receptor alpha Subunit
Kidney - pathology
Kidneys
Mice
Muscle contraction
Myocardium - pathology
Myofibroblasts
Renal failure
Review
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Summary:Fibrosis is a pathophysiological hallmark of cardiorenal disease. In the heart, fibrosis leads to contractile dysfunction and arrhythmias; in the kidney, it is the final common pathway for many diseases and predicts end‐stage renal failure. Despite this, there are currently no specific anti‐fibrotic treatments available for cardiac or renal disease. Recently and unexpectedly, IL‐11 was found to be of major importance for cardiorenal fibroblast activation and fibrosis. In mouse models, IL‐11 overexpression caused fibrosis of the heart and kidney while genetic deletion of Il11ra1 protected against fibrosis and preserved organ function. Neutralizing antibodies against IL‐11 or IL‐11RA have been developed that have anti‐fibrotic activity in human fibroblasts and protect against fibrosis in murine models of disease. While IL‐11 biology has been little studied and, we suggest, largely misunderstood, its autocrine activity in myofibroblasts appears non‐redundant for fibrosis, which offers new opportunities to better understand and potentially target cardiorenal fibrosis.
ISSN:0007-1188
1476-5381
DOI:10.1111/bph.15013