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Anakinra in Experimental Acute Myocardial Infarction—Does Dosage or Duration of Treatment Matter?

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Abstract

Purpose

Interleukin-1 (IL-1) receptor antagonist (Ra) is a naturally occurring IL-1 blocker with a cardioprotective effect during acute myocardial infarction (AMI). Anakinra, recombinant-human IL-1Ra, has been used to prevent heart failure in a mouse model of AMI. The aim of this study was to determine the optimal therapeutic regimen for anakinra in AMI.

Methods

We performed dose–response experiments comparing anakinra 1 mg/kg with 100 mg/kg doses, and duration–response experiments comparing 1-week to 2-week treatment. Echocardiography was used to assess cardiac remodeling and systolic function. Histopathology was used to detect apoptotic cardiomyocytes.

Results

A higher dose of anakinra was not associated with additional improvement in cardiac remodeling or function. The 2-week anakinra treatment had sustained and more favorable remodeling and systolic function compared to 1-week treatment with significantly smaller left ventricular end-systolic diameter and greater fractional shortening 4 weeks after AMI.

Conclusion

Anakinra inhibits apoptosis and ameliorates cardiac remodeling up to 4 weeks after infarction. A 2-week regimen is superior to a 1-week regimen, whereas a higher dose did not provide any further benefit over standard doses.

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Acknowledgements

The authors wish to thank Drs. David Crossman (University of Sheffield, UK), Charles Dinarello (University of Colorado, Denver, CO), Douglas Mann (Baylor College of Medicine, Houston, TX), and Benjamin Van Tassell (Virginia Commonwealth University, Richmond, VA) for critically discussing the data with the investigators. The authors wish also to thank Dr. Vera Di Trocchio (Virginia Commonwealth University, Richmond, VA) for her editorial assistance.

Disclosures

The drug (anakinra) used in the experiments was kindly provided by Amgen Inc. at no cost. None of the investigators have potential conflict of interests inherent to this study.

Sources of funding

This study was supported by the Thomas F. Jeffress and Kate Miller Jeffress Trust award, a Societa' Italiana di Cardiologia training grant, and the Mid-Atlantic Affiliate American Heart Association Beginning Grant-in-Aid to Dr. Abbate.

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Authors and Affiliations

  1. VCU Pauley Heart Center, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA, USA

    Fadi N. Salloum, Vinh Chau, Amit Varma, Nicholas N. Hoke, Stefano Toldo, George W. Vetrovec & Antonio Abbate

  2. Institute of Cardiology, Catholic University, Rome, Italy

    Stefano Toldo, Filippo Crea & Antonio Abbate

  3. Division of Cardiology, University of Turin, Turin, Italy

    Giuseppe G. L. Biondi-Zoccai

  4. Division of Cardiology/VCU Pauley Heart Center, Virginia Commonwealth University, 1200 East Broad Street-West Hospital, 10th Floor, East Wing, Room 1041, P.O. Box 980281, Richmond, VA, 23298-0281, USA

    Antonio Abbate

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  1. Fadi N. Salloum
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Correspondence to Antonio Abbate.

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Salloum, F.N., Chau, V., Varma, A. et al. Anakinra in Experimental Acute Myocardial Infarction—Does Dosage or Duration of Treatment Matter?. Cardiovasc Drugs Ther 23, 129–135 (2009). https://doi.org/10.1007/s10557-008-6154-3

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  • DOI: https://doi.org/10.1007/s10557-008-6154-3

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