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IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with...

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Autores principales: Gorelik, M., Lee, Y., Abe, M., Andrews, T., Davis, L., Patterson, J., Chen, S., Crother, T. R., Aune, G. J., Noval Rivas, M., Arditi, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718290/
https://www.ncbi.nlm.nih.gov/pubmed/31099056
http://dx.doi.org/10.1111/cei.13314
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author Gorelik, M.
Lee, Y.
Abe, M.
Andrews, T.
Davis, L.
Patterson, J.
Chen, S.
Crother, T. R.
Aune, G. J.
Noval Rivas, M.
Arditi, M.
author_facet Gorelik, M.
Lee, Y.
Abe, M.
Andrews, T.
Davis, L.
Patterson, J.
Chen, S.
Crother, T. R.
Aune, G. J.
Noval Rivas, M.
Arditi, M.
author_sort Gorelik, M.
collection PubMed
description Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first‐line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)‐1 receptor antagonist (IL‐1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG‐resistant patients. In this study, we sought to investigate the effect of IL‐1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell‐wall extract (LCWE)‐induced murine model of KD vasculitis and investigated the effect of IL‐1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL‐1Ra pretreatment significantly reduced KD‐induced myocardial inflammation and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) release. Both MRI and echocardiographic studies on LCWE‐injected KD mice demonstrated that IL‐1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL‐1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.
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spelling pubmed-67182902019-09-06 IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis Gorelik, M. Lee, Y. Abe, M. Andrews, T. Davis, L. Patterson, J. Chen, S. Crother, T. R. Aune, G. J. Noval Rivas, M. Arditi, M. Clin Exp Immunol Original Articles Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first‐line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)‐1 receptor antagonist (IL‐1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG‐resistant patients. In this study, we sought to investigate the effect of IL‐1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell‐wall extract (LCWE)‐induced murine model of KD vasculitis and investigated the effect of IL‐1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL‐1Ra pretreatment significantly reduced KD‐induced myocardial inflammation and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) release. Both MRI and echocardiographic studies on LCWE‐injected KD mice demonstrated that IL‐1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL‐1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD. John Wiley and Sons Inc. 2019-06-21 2019-10 /pmc/articles/PMC6718290/ /pubmed/31099056 http://dx.doi.org/10.1111/cei.13314 Text en © 2019 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Gorelik, M.
Lee, Y.
Abe, M.
Andrews, T.
Davis, L.
Patterson, J.
Chen, S.
Crother, T. R.
Aune, G. J.
Noval Rivas, M.
Arditi, M.
IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis
title IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis
title_full IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis
title_fullStr IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis
title_full_unstemmed IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis
title_short IL‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis
title_sort il‐1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of kawasaki disease vasculitis and myocarditis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718290/
https://www.ncbi.nlm.nih.gov/pubmed/31099056
http://dx.doi.org/10.1111/cei.13314
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