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

Abstract

Interleukin-33 is a newly recognized cytokine of the IL-1 family. Unlike its other members IL-1α, IL-1β 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.

interleukin‐33 - soluble and membrane‐anchored ST2L receptor - angiogenesis - biomechanical strain - congestive heart failure - myocardial infarction

References

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Addendum

Since ST2/IL33 is an extraordinarily vast topic which extends into virtually all fields of contemporary medicine, ours is only a modest contribution designed to offer a basic up-to-date overview to the cardiac surgeon who, as we know from our own experience, is an extremely busy man or woman. This theme may be promising for the future, just as it may prove to be a blind alley. Personally, we believe the former. Due to the constraints of time and space, we were not able to treat the topic in full length or to exploit all the available relevant literature. For the interested reader, we have included some of the latest reviews and papers of extraordinary quality. Other papers will undoubtedly follow. Whether they will be directed predominantly at immunologists or also at cardiologists/cardiac surgeons is hard to tell. Owing to the fact that immunology and molecular biology affect all medical fields, we hope that the time spent in reading this article will not be “le temps perdu”.

Additional Reading

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• 45 Wood I S, Wang B, Trayhurn P. IL-33, a recently identified interleukin-1 gene family member, is expressed in human adipocytes.  Biochem Biophys Res Commun. 2009;  384 105-109
• 46 Weinberg E O. ST2 protein in heart disease: from discovery to mechanisms and prognostic value.  Biomarkers Med. 2009;  3 495-511
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