Ethyl Pyruvate Ameliorates Experimental Autoimmune Myocarditis
Abstract:
Ethyl pyruvate (EP) has profound anti-inflammatory and immunomodulatory properties.
Here, its effects were determined on experimental autoimmune myocarditis (EAM) induced in mice
by heart-specific myosin-alpha heavy chain peptide immunization. EP was applied intraperitoneally,
daily, starting with the immunization. Severity of EAM was determined by histological assessment
of immune cell infiltrates into the heart. Cells were phenotypically characterized by flow cytometry.
Concentration of cytokines in cell culture supernatants and sera was determined by ELISA.
EP reduced the infiltration of immune cells into the heart and lessened heart inflammation. Smaller
number of total immune cells, as well as of CD11b+ and CD11c+ cells were isolated from the hearts of
EP-treated mice. A reduced number of antigen-presenting cells, detected by anti-CD11c, MHC class
II and CD86 antibodies, as well as of T helper (Th)1 and Th17 cells, detected by anti-CD4, IFN-
and
IL-17 antibodies, was determined in mediastinal lymph nodes draining the heart, in parallel. In the
spleen, only the number of CD11c+ cells were reduced, but not of the other examined populations,
thus implying limited systemic effect of EP. Reduced production of IFN-
and IL-17 by myosin-alpha
heavy chain peptide-restimulated cells of the lymph nodes draining the site of immunization was
observed in EP-treated mice. Our results clearly imply that EP restrains autoimmunity in EAM.
Therapeutic application of EP in the treatment of myocarditis in humans should be addressed in the
forthcoming studies.
Keywords:
myocarditis; ethyl pyruvate; inflammation; interleukin-17; interferon-gammaSource:
Biomolecules, 2021, 11, 12, 1768-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/biom11121768
ISSN: 2218-273X