Mucosal tolerance induction in autoimmune myocarditis and myocardial infarction
Background - Antigen-specific therapy is a compelling approach for the treatment of autoimmune conditions. Primary goal is to induce the specific tolerization of self-reactive immune cells without altering host immunity against pathogens. We studied the effects of mucosal tolerance induction on cTnI...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2013
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| In: |
International journal of cardiology
Year: 2013, Volume: 162, Issue: 3, Pages: 245-252 |
| ISSN: | 1874-1754 |
| DOI: | 10.1016/j.ijcard.2011.05.057 |
| Online Access: | lizenzpflichtig lizenzpflichtig 
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| Author Notes: | Jin Li, Stefan Göser, Florian Leuschner, H. Christian Volz, Sebastian Buss, Martin Andrassy, Renate Öttl, Gabriele Pfitzer, Hugo A. Katus, Ziya Kaya |
| Summary: | Background - Antigen-specific therapy is a compelling approach for the treatment of autoimmune conditions. Primary goal is to induce the specific tolerization of self-reactive immune cells without altering host immunity against pathogens. We studied the effects of mucosal tolerance induction on cTnI-induced experimental autoimmune myocarditis (EAM) and post-infarct remodeling. - Methods - Mucosal tolerance was induced by intranasal application of cTnI, alternatively anti-CD3 p.o. Protocols varied in frequency, dosage and time point of application before EAM. We then applied the most effective regimen to mice undergoing myocardial infarction in order to verify its effectiveness in post-infarct cardiac remodeling. The myocardium was evaluated on histological slides and for the cytokine secretion pattern, while echocardiography determined cardiac function. - Results - A single dose of 100μg of cTnI 7days prior to myocarditis appeared to be most effective in suppressing inflammation and fibrosis (p=0.03), while improving fractional shortening (p=0.02). Treatment with intranasal cTnI upregulated IL-10 expression. On the other hand, frequent intranasal application of high doses of cTnI increased myocardial inflammation. Anti-CD3 p.o. showed the propensity to reduce myocardial inflammation and improve cardiac function. The single dose regimen of i.n. cTnI applied 7days before a myocardial infarction reduced inflammation by trend (p=0.07) and improved heart function (p=0.002). Moreover, expression of matrix metalloproteinases 9 and 14 significantly decreased when treated with intranasal cTnI (p<0.01). - Conclusions - Depending on the optimal amount, the time period and the choice of antigen, effective mucosal tolerance can be achieved and represents an appealing therapeutic approach in the inflammatory process of cardiac remodeling. |
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| Item Description: | Available online 17 June 2011 Gesehen am 21.02.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1874-1754 |
| DOI: | 10.1016/j.ijcard.2011.05.057 |