CoChat
Sign Up
Cited by 69IL-33, ST2, and ILC PathwaysViral Infections and Immunology ResearchCardiac Fibrosis and Remodeling

IL-33 Independently Induces Eosinophilic Pericarditis and Cardiac Dilation: ST2 Improves Cardiac Function

Open access
Abston, Eric D., Barin, Jobert G., Cihakova, Daniela, Bucek, Adriana, Coronado, Michael J., Brandt, Jessica E., Bedja, Djahida, Kim, Joseph B. +4 more·2012·Circulation: Heart Failure
DOI 10.1161/circheartfailure.111.963769PMC PMC3874395
Open this paper in CoChat — free accountOpen PDF

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-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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/circheartfailure.111.963769

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Autoantibodies against α-MyHC are detected in mice with eosinophilic myopericarditis induced by recombinant IL-33 administration.

    “autoantibodies against α -MyHC have been detected in mice with eosinophilic myopericarditis, which involves inflamed myocardium and pericardium, induced by recombinant IL-33 in vivo administration.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [209]

    The Results section, “IL-33 increases eosinophilic perimyocarditis without affecting virus levels” (page unavailable), reports that recombinant IL-33 increased myocarditis, pericarditis, and cardiac eosinophils in CVB3-infected mice. The paper does not report detecting autoantibodies against α-MyHC in those mice; searches for α-MyHC and cardiac-myosin autoantibodies found no such result. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 39

  1. [1]O'Connell JB The role of myocarditis in end-stage dilated cardiomyopathy Tex Heart Inst J 1987 14 268 275 15227310 PMC324736
  2. [2]Cooper LT Jr Myocarditis N Engl J Med 2009 360 1526 1538 19357408 PMC5814110
  3. [3]Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TM Carnethon MR Dai S de Simone G Ford ES Fox CS Fullerton HJ Gillespie C Greenlund KJ Hailpern SM Heit JA Ho PM Howard VJ Kissela BM Kittner SJ Lackland DT Lichtman JH Lisabeth LD Makuc DM Marcus GM Marelli A Matchar DB McDermott MM Meigs JB Moy CS Mozaffarian D Mussolino ME Nichol G Paynter NP Rosamond WD Sorlie PD Stafford RS Turan TN Turner MB Wong ND Wylie-Rosett J American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart disease and stroke statistics- 2011 update Circulation 2011 123 e18 e209 21160056 PMC4418670
  4. [4]Fairweather D Rose NR Coxsackievirus-induced myocarditis in mice: a model of autoimmune disease for studying immunotoxicity Methods 2007 41 118 122 17161308 PMC1764911
  5. [5]Afanasyeva M Wang Y Kaya Z Park S Zilliox MJ Schofield BH Hill SL Rose NR Experimental autoimmune myocarditis in A/J mice is an interleukin-4-dependent disease with a Th2 phenotype Am J Pathol 2001 159 193 203 11438466 PMC1850414
  6. [6]Fairweather D Frisancho-Kiss S Yusung SA Barrett MA Gatewood SJL Davis SE Njoku DB Rose NR IFN-γ protects against chronic viral myocarditis by reducing mast cell degranulation, fibrosis, and the profibrotic cytokines TGF-β1, IL-1β, and IL-4 in the heart Am J Pathol 2004 165 1883 1894 15579433 PMC1618717
  7. [7]Torre-Amione G Kapadia S Benedict C Oral H Young JB Mann DL Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD) J Am Coll Cardiol 1996 27 1201 1206 8609343
  8. [8]Lane JR Neumann DA Lafond-Walker A Herskowitz A Rose NR Role of IL-1 and tumor necrosis factor in coxsackie virus-induced autoimmune myocarditis J Immunol 1993 151 1682 1690 8335952
  9. [9]Hedayat M Mahmoudi MJ Rose NR Rezaei N Proinflammatory cytokines in heart failure: double-edged swords Heart Fail Rev 2010 15 543 562 20405319
  10. [10]Liew FY Pitman NI McInnes IB Disease-associated functions of IL-33: the new kid in the IL-1 family Nat Rev Immunol 2010 10 103 110 20081870
  11. [11]Matsuyama Y Okazaki H Hoshino M Onishi S Kamata Y Nagatani K Nagashima T Iwamoto M Yoshio T Ohto-Ozaki H Tamemoto H Komine M Sekiya H Tominaga SI Minota S Increased levels of interleukin 33 in sera and synovial fluid from patients with active rheumatoid arthritis J Rheumatol 2010 37 18 25 19918048
  12. [12]Xu D Jiang HR Kewin P Li Y Mu R Fraser AR Pitman N Kurowska-Stolarska M McKenzie AN McInnes IB Liew FY IL-33 exacerbates antigen-induced arthritis by activating mast cells Proc Natl Acad Schi USA 2008 105 10913 10918 PMC2491487 18667700
  13. [13]Xu D Jiang HR Pushparaj PN Kurowska-Stolarska M Leung BP Mu R Tay HK McKenzie AN McInnes IB Melendez AJ Liew FY IL-33 exacerbates autoantibody-induced arthritis J Immunol 2010 184 2620 2626 20139274
  14. [14]Sanada S Hakuno D Hiqqins LJ Schreiter ER McKenzie AN Lee RT IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system J Clin Invest 2007 117 1538 1549 17492053 PMC1865027
  15. [15]Seki K Sanada S Kudinova AY Steinhauser ML Handa V Gannon J Lee RT Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling Circ Heart Fail 2009 2 684 691 19919994
  16. [16]Georgakopoulos D Kass DA Protocols for hemodynamic assessment of transgenic mice in vivo Methods Mol Biol 2003 219 233 243 12597013
  17. [17]Pacher P Nagayama T Mukhopadhyay P Batkai S Kass DA Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats Nat Protocols 2008 3 1422 1434 PMC2597499 18772869
  18. [19]Lorenz JN Robbins J Measurement of intraventricular pressure and cardiac performance in the intact closed-chest anesthetized mouse Am J Physiol 1997 272 H1137 H1146 9087586
  19. [20]Gyurko R Kuhlencordt P Fishman MC Huang PL Modulation of mouse cardiac function in vivo by eNOS and ANP Am J Physiol Heart Circ Physiol 2000 278 H971 H981 10710367
  20. [22]Barin JG Talor MV Baldeviano GC Kimura M Rose NR Cihakova D Mechanisms of IFNγ regulation of autoimmune myocarditis Exp Mol Pathol 2010 89 83 91 20599938 PMC4266481
  21. [23]Baldeviano GC Barin JG Talor MV Srinivasa S Bedja D Zheng D Gabrielson K Iwakura Y Rose NR Cihakova D Interleukin-17A is dispensable for myocarditis but essential for progression to dilated cardiomyopathy Circ Res 2010 106 1646 1655 20378858
  22. [25]Miller AM Liew FY The IL-33/ST2 pathway- a new therapeutic target in cardiovascular disease Pharmacol Ther 2011 131 179 186 21356240
  23. [26]Prabhu SD Cytokine-induced modulation of cardiac function Circ Res 2004 95 1140 1153 15591236
  24. [27]Lamba S Abraham WT Alterations in adrenergic receptor signaling in heart failure Heart Fail Rev 2000 5 7 16 16228912
  25. [28]Funakoshi H Kubota T Kawamura N Machida Y Feldman AM Tsutsui H Shimokawa H Takeshita A Disruption of inducible nitric oxide synthase improves beta-adrenergic inotropic responsiveness but not the survival of mice with cytokine-induced cardiomyopathy Circ Res 2002 90 959 965 12016261
  26. [29]Pecaric-Petkovic T Didichenko SA Kaempfer S Spiegl N Dahinden CA Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33 Blood 2009 113 1526 1534 18955562 PMC2644080
  27. [30]Joshi AD Oak SR Hartigan AJ Finn WG Kunkel SL Duffy KE Das A Hogaboam CM Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages BMC Immunol 2010 11 52 20958987 PMC2967528
  28. [31]Pastorelli L Garq RR Hoang SB Spina L Mattioli B Scarpa M Fiocchi C Vecchi M Pizarro TT Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis Proc Natl Acad Sci USA 2010 107 8017 8022 20385815 PMC2867895
  29. [32]Weinberg EO Shimpo M Hurwitz S Tominaga S Rouleau JL Lee RT Identification of serum soluble ST2 receptor as a novel heart failure biomarker Circulation 2003 107 721 726 12578875
  30. [33]Fairweather D Yusung S Frisancho S Barrett M Gatewood S Steele R Rose NR IL-12Rβ1 and TLR4 increase IL-1β and IL-18-associated myocarditis and coxsackievirus replication J Immunol 2003 170 4731 4737 12707353
  31. [34]Afanasyeva M Georgakopoulos D Fairweather D Caturegli P Kass DA Rose NR Novel model of constrictive pericarditis associated with autoimmune heart disease in interferon-γ-knockout mice Circulation 2004 110 2910 2917 15505106
  32. [35]Rezaizadeh H Sanchez-Ross M Kaluski E Klapholz M Haider B Gerula C Acute eosinophilic myocarditis: diagnosis and treatment Acute Cardiac Care 2010 12 31 36 20201659
  33. [36]Kleinfeldt T Nienaber CA Kische S Akin I Turan RG Korber T Schneider H Ince H Cardiac manifestation of the hypereosinophilic syndrome: new insights Clin Res Cardiol 2010 99 419 427 20333409
  34. [37]Stolarski B Kurowska-Stolarska M Kewin P Xu D Liew FY IL-33 exacerbates eosinophil-mediated airway inflammation J Immunol 2010 185 3472 3480 20693421
  35. [38]Eichenholz PW Eichacker PQ Hoffman WD Banks SM Parrillo JE Danner RL Natanson C Tumor necrosis factor challenges in canines: patterns of cardiovascular dysfunction Am J Physiol 1992 263 H668 H675 1415590
  36. [39]Li C Zienkiewicz J Hawiger J Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain responsible for coupling to the IL1beta signaling pathway J Biol Chem 2005 280 26152 26159 15849357
  37. [40]Blyszczuk P Kania G Dieterle T Marty RR Valaperti A Berthonneche C Pedrazzini T Berger CT Dirnhofer S Matter CM Penninger JM Lüscher TF Eriksson U Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy Circ Res 2009 105 912 920 19762681
  38. [41]Bozkurt B Kribbs SB Clubb FJ Jr Michael LH Didenko VV Hornsby PJ Seta Y Oral H Spinale FG Mann DL Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats Circulation 1998 97 1382 1391 9577950
  39. [42]Liu SJ Zhou W Kennedy RH Suppression of beta-adrenergic responsiveness of L-type Ca2+ current by IL-1beta in rat ventricular myocytes Am J Physiol 1999 276 H141 H148 9887027

Cited by

Sorted by citations

Authors
Abston, E. D., Barin, J. G., Cihakova, D., Bucek, A., Coronado, M. J., Brandt, J. E., Bedja, D., Kim, J. B., Georgakopoulos, D., Gabrielson, K. L., Mitzner, W., & Fairweather, D.
Affiliations
  • Johns Hopkins University (US)
  • From the Department of Environmental Health Sciences (E.D.A., A.B., M.J.C., J.E.B., J.B.K., W.M., D.F.), the W. Harry Feinstone Department of Molecular Microbiology and Immunology (J.G.B.), Department of Pathology (D.C., D.F.), and Department of Molecular and Comparative Pathobiology (D.B., K.L.G.), Johns Hopkins University Bloomberg School of Public Health and School of Medicine, Baltimore, MD; and CVRx Inc, Minneapolis, MN (D.G.).
ORCID
Venue
Circulation: Heart Failure
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-05
Volume
5
Issue
3
Pages
366-375
ISSN
  • 1941-3289 (ISSN-L)
  • 1941-3297
DOI
10.1161/circheartfailure.111.963769
PMC
PMC3874395
OpenAlex
W1988596418
Cited by
69
References
3
Citations by year
2026: 5 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 3 · 2020: 11 · 2019: 2 · 2018: 5 · 2016: 1 · 2015: 1 · 2014: 7 · 2013: 6 · 2012: 3
FWCI
2.38
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Circulation Heart Failure (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R56HL077611, R01HL087033)
  • National Center for Research Resources (UL1RR025005)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
IL-33, ST2, eosinophilia, dilated cardiomyopathy, autoimmune heart disease, cardiac function, ventriculomegaly, IL-1β, interleukin-6, IL-4
MeSH terms
Interleukin-33, Interleukin-1 Receptor-Like 1 Protein, Animals, Autoimmune Diseases, Cardiomyopathy, Dilated, Coxsackievirus Infections, Disease Models, Animal, Eosinophilia, Heart, Interleukins, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Myocardium, Pericarditis, Recombinant Proteins, Interleukin-6, Receptors, Interleukin, Mice, Knockout, Mice, Interleukin-1beta

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review