Publication

Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion

Hartman, M. H. T., Vreeswijk-Baudoin, I., Groot, H. E., van de Kolk, K. W. A., de Boer, R. A., Leach, I. M., Vliegenthart, R., Sillje, H. H. W. & van der Harst, P., 9-Dec-2016, In : PLoS ONE. 11, 12, 11 p., e0167195.

Research output: Contribution to journalArticleAcademicpeer-review

Background

Interleukin-6 (IL-6) levels are upregulated in myocardial infarction. Recent data suggest a causal role of the IL-6 receptor (IL-6R) in coronary heart disease. We evaluated if IL-6R blockade by a monoclonal antibody (MR16-1) prevents the heart from adverse left ventricular remodeling in a mouse model of ischemia-reperfusion (I/R).

Methods

CJ57/BL6 mice underwent I/R injury (left coronary artery ligation for 45 minutes) or sham surgery, and thereafter received MR16-1 (2mg/mouse) 5 minutes before reperfusion and 0.5mg/mouse weekly during four weeks, or control IgG treatment. Cardiac Magnetic Resonance Imaging (CMR) and hemodynamic measurements were performed to determine cardiac function after four weeks.

Results

I/R caused left ventricular dilatation and a decrease in left ventricular ejection fraction (LVEF). However, LVEF was significantly lower in the MR16-1 treatment group compared to the IgG group (28 +/- 4% vs. 35 +/- 6%, p = 0.02; sham 45 +/- 6% vs. 43 +/- 4%, respectively; p = NS). Cardiac relaxation (assessed by dP/dT) was not significantly different between the MR16-1 and IgG groups. Also, no differences were observed in histological myocardial fibrosis, infarct size and myocyte hypertrophy between the groups.

Conclusion

Blockade of the IL-6R receptor by the monoclonal MR16-1 antibody for four weeks started directly after I/R injury did not prevent the process of cardiac remodeling in mice, but rather associated with a deterioration in the process of adverse cardiac remodeling.

Original languageEnglish
Article numbere0167195
Number of pages11
JournalPLoS ONE
Volume11
Issue number12
Publication statusPublished - 9-Dec-2016

    Keywords

  • RHEUMATOID-ARTHRITIS, IL-6 RECEPTOR, ANTIBODY, DISEASE, HEART, MICE, MECHANISMS, INFARCTION, CARDIOMYOCYTES, TOCILIZUMAB

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