Erythropoietin attenuates the development of experimental autoimmune myocarditis

Sho Ichi Hirose, Masafumi Takahashi, Ryo Ogawa, Hajime Morimoto, Atsushi Izawa, Hajime Sato, Hirohiko Ise, Minoru Hongo, Uichi Ikeda

Research output: Contribution to journalArticle

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Abstract

Objective: 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). Methods and results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)17-27
Number of pages11
JournalCardiovascular Drugs and Therapy
Volume21
Issue number1
DOIs
Publication statusPublished - Feb 1 2007
Externally publishedYes

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Myocarditis
Erythropoietin
Cytokines
Lymphocytes
Inflammation
Myocardium
Cardiac Myosins
Mast Cells
Autoimmune Diseases
Real-Time Polymerase Chain Reaction
Anti-Inflammatory Agents
Theoretical Models
Swine
Immunohistochemistry
Macrophages
Body Weight
Blood Pressure
T-Lymphocytes
Antigens
Weights and Measures

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Hirose, S. I., Takahashi, M., Ogawa, R., Morimoto, H., Izawa, A., Sato, H., ... Ikeda, U. (2007). Erythropoietin attenuates the development of experimental autoimmune myocarditis. Cardiovascular Drugs and Therapy, 21(1), 17-27. https://doi.org/10.1007/s10557-007-6005-7

Erythropoietin attenuates the development of experimental autoimmune myocarditis. / Hirose, Sho Ichi; Takahashi, Masafumi; Ogawa, Ryo; Morimoto, Hajime; Izawa, Atsushi; Sato, Hajime; Ise, Hirohiko; Hongo, Minoru; Ikeda, Uichi.

In: Cardiovascular Drugs and Therapy, Vol. 21, No. 1, 01.02.2007, p. 17-27.

Research output: Contribution to journalArticle

Hirose, SI, Takahashi, M, Ogawa, R, Morimoto, H, Izawa, A, Sato, H, Ise, H, Hongo, M & Ikeda, U 2007, 'Erythropoietin attenuates the development of experimental autoimmune myocarditis', Cardiovascular Drugs and Therapy, vol. 21, no. 1, pp. 17-27. https://doi.org/10.1007/s10557-007-6005-7
Hirose, Sho Ichi ; Takahashi, Masafumi ; Ogawa, Ryo ; Morimoto, Hajime ; Izawa, Atsushi ; Sato, Hajime ; Ise, Hirohiko ; Hongo, Minoru ; Ikeda, Uichi. / Erythropoietin attenuates the development of experimental autoimmune myocarditis. In: Cardiovascular Drugs and Therapy. 2007 ; Vol. 21, No. 1. pp. 17-27.
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