TY - JOUR
T1 - IL-33 independently induces eosinophilic pericarditis and cardiac dilation ST2 improves cardiac function
AU - Abston, Eric D.
AU - Barin, Jobert G.
AU - Cihakova, Daniela
AU - Bucek, Adriana
AU - Coronado, Michael J.
AU - Brandt, Jessica E.
AU - Kim, Djahida Bedjajoseph B.
AU - Georgakopoulos, Dimitrios
AU - Gabrielson, Kathleen L.
AU - Mitzner, Wayne
AU - Fairweather, Delisa
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Cytokines
KW - Eosinophils
KW - Idiopathic dilated cardiomyopathy
KW - Inflammation
KW - Myocarditis
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U2 - 10.1161/CIRCHEARTFAILURE.111.963769
DO - 10.1161/CIRCHEARTFAILURE.111.963769
M3 - Article
C2 - 22454393
AN - SCOPUS:84864325315
SN - 1941-3289
VL - 5
SP - 366
EP - 375
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 3
ER -