IL-33 independently induces eosinophilic pericarditis and cardiac dilation ST2 improves cardiac function

Eric D. Abston, Jobert G. Barin, Daniela Cihakova, Adriana Bucek, Michael J. Coronado, Jessica E. Brandt, Djahida Bedjajoseph B. Kim, Dimitrios Georgakopoulos, Kathleen L. Gabrielson, Wayne Mitzner, Delisa Fairweather

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background-IL-33 through its receptor ST2 protects the heart from myocardial infarct and hypertrophy in animal models but, paradoxically, increases autoimmune disease. In this study, we examined the effect of IL-33 or ST2 administration on autoimmune heart disease. Methods and Results-We used pressure-volume relationships and isoproterenol challenge to assess the effect of recombinant (r) IL-33 or rST2 (eg, soluble ST2) administration on the development of autoimmune coxsackievirus B3 myocarditis and dilated cardiomyopathy in male BALB/c mice. The rIL-33 treatment significantly increased acute perimyocarditis (P 0.006) and eosinophilia (P 1.3 10 5), impaired cardiac function (maximum ventricular power, P 0.0002), and increased ventricular dilation (end-diastolic volume, P 0.01). The rST2 treatment prevented eosinophilia and improved heart function compared with rIL-33 treatment (ejection fraction, P 0.009). Neither treatment altered viral replication. The rIL-33 treatment increased IL-4, IL-33, IL-1, and IL-6 levels in the heart during acute myocarditis. To determine whether IL-33 altered cardiac function on its own, we administered rIL-33 to undiseased mice and found that rIL-33 induced eosinophilic pericarditis and adversely affected heart function. We used cytokine knockout mice to determine that this effect was due to IL-33-mediated signaling but not to IL-1 or IL-6. Conclusions-We show for the first time to our knowledge that IL-33 induces eosinophilic pericarditis, whereas soluble ST2 prevents eosinophilia and improves systolic function, and that IL-33 independently adversely affects heart function through the IL-33 receptor.

Original languageEnglish (US)
Pages (from-to)366-375
Number of pages10
JournalCirculation: Heart Failure
Issue number3
StatePublished - May 2012


  • Cytokines
  • Eosinophils
  • Idiopathic dilated cardiomyopathy
  • Inflammation
  • Myocarditis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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