Interleukin-33, a Novel Member of the IL-1/IL-18 Cytokine Family, in Cardiology and Cardiac Surgery

Interleukin-33 is a newly recognized cytokine of the IL-1 family. Unlike its other members IL-1 alpha, IL-1 beta and IL-18, interleukin-33 induces predominantly Th2-skewed immune responses. In this context, the effects of IL-33 are mostly anti-inflammatory. However, depending on the actual cytokine and cellular milieu, IL-33 can promote both Th1 and Th2 immune reactions. Most importantly for cardiology and cardiac surgery, IL-33 has emerged to represent the as yet unknown ligand of the orphan receptor ST2. Before the advent of IL-33, the ST2 receptor, currently recognized as the soluble one of its two isoforms, was considered to be an unfavorable prognostic marker in myocardial infarction, congestive heart failure and trauma/sepsis shock patients. Now we know that IL-33, when bound to the cellular membrane-anchored ST2L isoform of the receptor, can have certain beneficial effects on the aforementioned conditions. Various forms of IL-33 interaction with the respective isoforms of its cognate receptor are discussed here. The focus is on physiological and prognostic values in cardiac patients.