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

The recent discovery of the ST2 receptor ligand — interleukin-33 — has provided new insight into the importance of ST2 signalling as a mediator of inflammation. Now, an additional role for this pathway as a novel cardioprotective paracrine system is emerging. Here, Kakkar and Lee review these roles and discuss the therapeutic potential of targeting this pathway to treat associated diseases such as asthma, rheumatoid arthritis, atherosclerosis and heart failure. 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.