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Nature Reviews Drug Discovery 7, 827–840 (1 October 2008) | doi:10.1038/nrd2660

The IL-33/ST2 pathway: therapeutic target and novel biomarker

Rahul Kakkar & Richard T. Lee

For many years, the interleukin-1 receptor family member ST2 was an orphan receptor that was studied in the context of inflammatory and autoimmune disease. However, in 2005, a new cytokine — interleukin-33 (IL-33) — was identified as a functional ligand for ST2. IL-33/ST2 signalling is involved in T-cell mediated immune responses, but more recently, an unanticipated role in cardiovascular disease has been demonstrated. IL-33/ST2 not only represents a promising cardiovascular biomarker but also a novel mechanism of intramyocardial fibroblast–cardiomyocyte communication that may prove to be a therapeutic target for the prevention of heart failure.