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 A Mitzner, Delisa Fairweather

Research output: Contribution to journalArticle

Abstract

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
Volume5
Issue number3
DOIs
StatePublished - May 2012

Fingerprint

Pericarditis
Dilatation
Eosinophilia
Myocarditis
Interleukin-1
Autoimmune Diseases
Interleukin-6
Interleukin-33
Ventricular Function
Enterovirus
Dilated Cardiomyopathy
Isoproterenol
Knockout Mice
Interleukin-4
Stroke Volume
Hypertrophy
Heart Diseases
Animal Models
Myocardial Infarction
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

IL-33 independently induces eosinophilic pericarditis and cardiac dilation ST2 improves cardiac function. / Abston, Eric D.; Barin, Jobert G.; Cihakova, Daniela; Bucek, Adriana; Coronado, Michael J.; Brandt, Jessica E.; Kim, Djahida Bedjajoseph B; Georgakopoulos, Dimitrios; Gabrielson, Kathleen L; Mitzner, Wayne A; Fairweather, Delisa.

In: Circulation: Heart Failure, Vol. 5, No. 3, 05.2012, p. 366-375.

Research output: Contribution to journalArticle

Abston, Eric D. ; Barin, Jobert G. ; Cihakova, Daniela ; Bucek, Adriana ; Coronado, Michael J. ; Brandt, Jessica E. ; Kim, Djahida Bedjajoseph B ; Georgakopoulos, Dimitrios ; Gabrielson, Kathleen L ; Mitzner, Wayne A ; Fairweather, Delisa. / IL-33 independently induces eosinophilic pericarditis and cardiac dilation ST2 improves cardiac function. In: Circulation: Heart Failure. 2012 ; Vol. 5, No. 3. pp. 366-375.
@article{a05999fcfe164dbeaccf8449d93b6601,
title = "IL-33 independently induces eosinophilic pericarditis and cardiac dilation ST2 improves cardiac function",
abstract = "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.",
keywords = "Cytokines, Eosinophils, Idiopathic dilated cardiomyopathy, Inflammation, Myocarditis",
author = "Abston, {Eric D.} and Barin, {Jobert G.} and Daniela Cihakova and Adriana Bucek and Coronado, {Michael J.} and Brandt, {Jessica E.} and Kim, {Djahida Bedjajoseph B} and Dimitrios Georgakopoulos and Gabrielson, {Kathleen L} and Mitzner, {Wayne A} and Delisa Fairweather",
year = "2012",
month = "5",
doi = "10.1161/CIRCHEARTFAILURE.111.963769",
language = "English (US)",
volume = "5",
pages = "366--375",
journal = "Circulation: Heart Failure",
issn = "1941-3297",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

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 A

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

UR - http://www.scopus.com/inward/record.url?scp=84864325315&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864325315&partnerID=8YFLogxK

U2 - 10.1161/CIRCHEARTFAILURE.111.963769

DO - 10.1161/CIRCHEARTFAILURE.111.963769

M3 - Article

C2 - 22454393

AN - SCOPUS:84864325315

VL - 5

SP - 366

EP - 375

JO - Circulation: Heart Failure

JF - Circulation: Heart Failure

SN - 1941-3297

IS - 3

ER -