Interleukin-1 trap attenuates cardiac remodeling after experimental acute myocardial infarction in mice.
BACKGROUND
Interleukin-1 (IL-1) is an inflammatory cytokine that responds as an acute phase reactant during acute myocardial infarction. Conflicting data describe the role of anti-IL-1 interventions to reduce cardiac remodeling after AMI. IL-1 Trap is a modified recombinant fusion protein that binds circulating IL-1. Our study evaluated the effects of murine IL-1 Trap on cardiac remodeling after AMI resulting from permanent surgical coronary artery ligation.


METHODS
Mice received treatment with intraperitoneal injection of murine IL-1 Trap (1 mg/kg [n = 5], 5 mg/kg [n = 5], or 30 mg/kg [n = 5]) or NaCl 0.9% (saline; n = 10) every 48 hours after surgery. Transthoracic echocardiography was performed at baseline and 7 days after surgery. Inhibition of IL-1 signaling was determined by measurement of IL-6 plasma levels (enzyme-linked immunosorbent assay) after IL-1b injection. Apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) was measured in murine heart samples and in a primary culture of murine cardiomyocytes.


RESULTS
Mice treated with 5 mg/kg or 30 mg/kg IL-1 Trap had more favorable cardiac remodeling and echocardiographic assessment of infarct size at 7 days compared with saline (P < 0.05 for each comparison). Treatment with IL-1 Trap also reduced apoptosis and IL-6 levels compared with saline treatment.


CONCLUSIONS
IL-1 Trap ameliorates cardiac remodeling and reduces cardiomyocyte apoptosis after experimental acute myocardial infarction in the mouse.
Van Tassell
Benjamin W
BW
Pauley Heart Center, Virginia Commonwealth University, Richmond, 23298-0281, USA.
Varma
Amit
A
Salloum
Fadi N
FN
Das
Anindita
A
Seropian
Ignacio M
IM
Toldo
Stefano
S
Smithson
Lisa
L
Hoke
Nicholas N
NN
Chau
Vinh Q
VQ
Robati
Roshanak
R
Abbate
Antonio
A
D000818:Animals; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000008:administration & dosage* / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
D053583:Interleukin-1beta; D011993:Recombinant Fusion Proteins; D000093242:Interleukin-6 Inhibitors; C531377:rilonacept