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 language||English (US)|
|Number of pages||10|
|Journal||Circulation: Heart Failure|
|State||Published - May 2012|
- Idiopathic dilated cardiomyopathy
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine