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.
  
  
  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-1β, 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-1β 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.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health and School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Abston
authors.forename: Jobert G
authors.initials: JG
authors.lastname: Barin
authors.forename: Daniela
authors.initials: D
authors.lastname: Cihakova
authors.forename: Adriana
authors.initials: A
authors.lastname: Bucek
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Coronado
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Brandt
authors.forename: Djahida
authors.initials: D
authors.lastname: Bedja
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Kim
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Georgakopoulos
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gabrielson
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.forename: DeLisa
authors.initials: D
authors.lastname: Fairweather
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000517:prevention & control / Q000821:virology; D002311:Cardiomyopathy, Dilated / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D003384:Coxsackievirus Infections / Q000150:complications; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology* / Q000517:prevention & control / Q000821:virology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D010493:Pericarditis / Q000209:etiology* / Q000517:prevention & control / Q000821:virology; D018123:Receptors, Interleukin / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta; D000067596:Interleukin-33; D015850:Interleukin-6; D007378:Interleukins; D018123:Receptors, Interleukin; D011994:Recombinant Proteins