Erythropoietin attenuates the development of experimental autoimmune myocarditis

• Published in: Cardiovascular drugs and therapy 2007-02, Vol.21 (1), p.17-27
• Main Authors: HIROSE, Sho-Ichi, TAKAHASHI, Masafumi, OGAWA, Ryo, MORIMOTO, Hajime, IZAWA, Atsushi, SATO, Hajime, ISE, Hirohiko, HONGO, Minoru, IKEDA, Uichi
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Autoimmune Diseases - blood; Autoimmune Diseases - chemically induced; Autoimmune Diseases - drug therapy; Biological and medical sciences; Blood Pressure - drug effects; Blotting, Western; Cardiac Myosins - administration & dosage; Cardiac Myosins - toxicity; Cardiology. Vascular system; Cardiovascular system; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Cytokines - classification; Cytokines - genetics; Cytokines - metabolism; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Heart; Hemoglobins - metabolism; Immunochemistry; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Male; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - metabolism; Medical sciences; Models, Animal; Myocarditis - drug therapy; Myocarditis - immunology; Myocarditis - physiopathology; Myocarditis. Cardiomyopathies; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Pharmacology. Drug treatments; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Receptors, Erythropoietin - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; Ventricular Function, Left - drug effects
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-007-6005-7

Erythropoietin (EPO) has been shown to not only have cardioprotective effects but also attenuate autoimmune diseases. In the present study, we investigated the effect of EPO on cardiac inflammation and function, inflammatory cell infiltration, and cytokine expression in a rat model of experimental autoimmune myocarditis (EAM). Male Lewis rats (6-8 weeks old) were immunized on day 0 with porcine cardiac myosin to establish EAM. The rats were subcutaneously administered either vehicle (saline) or human recombinant EPO (6,000 U/kg, 3 days/week) from day 0 to 20, and they were evaluated on day 21. In the EPO group, the inflammation area and heart weight/body weight ratio were significantly attenuated as compared with those in the vehicle group. Blood pressure and cardiac function were also improved in the EPO group. Immunohistochemistry revealed that EPO decreased the infiltration of macrophages and CD4 T cells, and degranulated mast cells in the myocardium. Real-time RT-PCR analysis demonstrated that inflammatory cytokine expression in the myocardium and lymphocytes was suppressed in the EPO group. However, in vitro experiments showed that EPO had no effect on antigen-induced proliferation and cytokine expression in lymphocytes. EPO attenuates inflammatory cell infiltration and cytokine expression, and it improves cardiac function and reduces cardiac inflammation in EAM. This beneficial effect of EPO is unlikely to arise from a direct anti-inflammatory action on lymphocytes. These findings suggest the therapeutic potential of EPO for the treatment of myocarditis.