title: Mucosal tolerance induction in autoimmune myocarditis and myocardial infarction.
abstract: 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 100 μg of cTnI 7 days 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 7 days 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.
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Stefan
authors.initials: S
authors.lastname: Göser
authors.forename: Florian
authors.initials: F
authors.lastname: Leuschner
authors.forename: H Christian
authors.initials: HC
authors.lastname: Volz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Buss
authors.forename: Martin
authors.initials: M
authors.lastname: Andrassy
authors.forename: Renate
authors.initials: R
authors.lastname: Öttl
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pfitzer
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Ziya
authors.initials: Z
authors.lastname: Kaya
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D006224:Cricetinae; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009203:Myocardial Infarction / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D009205:Myocarditis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D019210:Troponin I / Q000008:administration & dosage
chemical_list: D019210:Troponin I