title: Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
authors.forename: Minke H T
authors.identifier: http://orcid.org/0000-0002-6965-3259
authors.initials: MH
authors.lastname: Hartman
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Vreeswijk-Baudoin
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
authors.forename: Hilde E
authors.initials: HE
authors.lastname: Groot
authors.affiliation: University of Groningen, University Medical Center Groningen, the Central Animal Facility, Groningen, the Netherlands.
authors.forename: Kees W A
authors.initials: KW
authors.lastname: van de Kolk
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Mateo Leach
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Radiology, Groningen, the Netherlands.
authors.forename: Rozemarijn
authors.initials: R
authors.lastname: Vliegenthart
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Sillje
authors.affiliation: University of Groningen, University Medical Center Groningen, the department of Cardiology, Groningen, the Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006984:Hypertrophy / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6