Interleukin-6 receptor inhibition modulates the immune reaction and restores titin phosphorylation in experimental myocarditis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-10-25

AUTHORS

Konstantinos Savvatis, Irene Müller, Matthias Fröhlich, Kathleen Pappritz, Christin Zietsch, Nazha Hamdani, Karsten Grote, Bernhard Schieffer, Karin Klingel, Sophie Van Linthout, Wolfgang A. Linke, Heinz-Peter Schultheiss, Carsten Tschöpe

ABSTRACT

Increased levels of interleukin-6 (IL-6) have been observed in patients with acute myocarditis and are associated with poor prognosis. This study was designed to examine whether treatment with anti-IL-6 receptor antibody improves cardiac dysfunction and left ventricular (LV) remodeling in experimental Coxsackie virus B3 (CVB3)-induced myocarditis. C57BL6/J mice were subjected to acute CVB3 infection. One day after viral infection mice were treated with a single injection of an anti-IL-6 receptor antibody (MR16-1, tocilizumab) or control IgG. Seven days after viral infection, LV function was examined by conductance catheter technique, cardiac remodeling assessed by estimation of titin phosphorylation, cardiac fibrosis, and inflammatory and antiviral response by immunohistochemistry, RT-PCR and cell culture experiments. Compared to controls, infected mice displayed an impaired systolic and diastolic LV function associated with an increase in cardiac inflammation, fibrosis and impaired titin phosphorylation. IL-6 receptor blockade led to a shift of the immune response to a Th1 direction and significant reduction of viral load. In addition, cardiac immune response, extracellular matrix regulation and titin function improved, resulting in a preserved LV function. IL-6 receptor blockade exerts cardiac beneficial effects by antiviral and immunomodulatory actions after induction of an acute murine CVB3 virus myocarditis. More... »

PAGES

449

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00395-014-0449-2

DOI

http://dx.doi.org/10.1007/s00395-014-0449-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031574023

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25344085


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71 induction
72 infection
73 infection mice
74 inflammation
75 inhibition
76 injection
77 interleukin-6
78 interleukin-6 receptor inhibition
79 levels
80 load
81 matrix regulation
82 mice
83 myocarditis
84 patients
85 phosphorylation
86 poor prognosis
87 prognosis
88 reaction
89 receptor antibodies
90 receptor blockade
91 receptor inhibition
92 reduction
93 regulation
94 remodeling
95 response
96 shift
97 significant reduction
98 single injection
99 study
100 systolic
101 technique
102 titin function
103 titin phosphorylation
104 treatment
105 ventricular
106 viral infection
107 viral load
108 virus myocarditis
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