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Interleukin-1β induces a reversible cardiomyopathy in the mouse

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Abstract

Background

Inflammatory mediators play a key role in the development and progression of heart failure. Interleukin-1β (IL-1β) is a prototypical inflammatory cytokine that suppresses myocyte contractility following acute administration.

Methods

Healthy mice were randomly assigned to daily intraperitoneal injections of recombinant murine IL-1β (3 μg/kg in 0.2 ml) or matching volumes of NaCl 0.9 % solution (vehicle) for 15 days. Echocardiography was performed at baseline and 4 h (acute), followed by repeat measurements immediately prior to IL-1β or saline injections on days 5, 10, and 15 (chronic). Final echocardiography was performed on day 20 (5 days after last treatment). A subgroup of animals underwent isoproterenol challenge to evaluate contractile reserve at baseline, 4 h (acute), 15 days (chronic) and 20 days (recovery).

Results

IL-1β reduced left ventricular fractional shortening (LVFS) at 4 h versus vehicle (−24 vs. 0 %, respectively, P < 0.05). This reduction was maintained throughout chronic dosing at day 15. IL-1β-treated mice also showed impaired contractile reserve with a right shift of the dose-response curve to isoproterenol (P < 0.05) at 4 h and 15 days. By day 20, 5 days after stopping IL-1β, LVFS and contractile reserve had returned to baseline.

Conclusions

IL-1β induces a reversible contractile dysfunction associated with impaired response to β-receptor stimulation.

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Acknowledgments

Dr. Van Tassell is supported by an Institutional National Institute of Health K12 development grant. Dr. Mezzaroma is supported by an American Heart Association Post-doctoral Fellow Award. Dr. Abbate is supported by an American Heart Association Scientist Development Grant.

Conflict of interest

In the past 12 months, Dr. Abbate has received consultant fees from Biovitrum and XOMA, and has received research support from Novartis.

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Authors and Affiliations

  1. Pharmacotherapy and Outcome Sciences, School of Pharmacy, Richmond, USA

    Benjamin W. Van Tassell, Ignacio M. Seropian & Eleonora Mezzaroma

  2. Victoria Johnson Research Laboratory, Richmond, USA

    Benjamin W. Van Tassell, Ignacio M. Seropian, Stefano Toldo, Eleonora Mezzaroma & Antonio Abbate

  3. VCU Pauley Heart Center, School of Medicine, Virginia Commonwealth University, 1200 E Broad Street, Box 980533, Richmond, VA, 23298, USA

    Benjamin W. Van Tassell, Stefano Toldo & Antonio Abbate

Authors
  1. Benjamin W. Van Tassell
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  2. Ignacio M. Seropian
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  3. Stefano Toldo
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  4. Eleonora Mezzaroma
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  5. Antonio Abbate
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Corresponding author

Correspondence to Benjamin W. Van Tassell.

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Responsible Editor: John Di Battista.

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Van Tassell, B.W., Seropian, I.M., Toldo, S. et al. Interleukin-1β induces a reversible cardiomyopathy in the mouse. Inflamm. Res. 62, 637–640 (2013). https://doi.org/10.1007/s00011-013-0625-0

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  • DOI: https://doi.org/10.1007/s00011-013-0625-0

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