A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice

PLoS One. 2015 Mar 13;10(3):e0119360. doi: 10.1371/journal.pone.0119360. eCollection 2015.

Abstract

Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22). Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis.

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / pathology*
  • Cell Proliferation / drug effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Disease Models, Animal
  • Fibrosis
  • Heart / drug effects
  • Heart / physiopathology
  • Heart Function Tests
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / pathology
  • Linagliptin / pharmacology*
  • Linagliptin / therapeutic use
  • Lung / drug effects
  • Lung / pathology
  • Lymphocytes / drug effects
  • Lymphocytes / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis / drug therapy
  • Myocarditis / genetics
  • Myocarditis / pathology*
  • Organ Size / drug effects

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Linagliptin

Grant support

The authors received no specific funding for this work.