title: Immunosuppression with an interleukin-2 fusion protein leads to improved LV function in experimental ischemic cardiomyopathy.
abstract: Several cytokines are activated in chronic heart failure (CHF), including interleukin-2 (IL-2). IL-2 is important for the survival of regulatory T cells, as well as for the function of activated T cells. Its role in ischemic cardiomyopathy has not yet been investigated. We therefore studied left ventricular (LV) performance and remodeling in a rat model of myocardial infarction (MI) after treatment with an IL-2IgG2b fusion protein to stimulate IL-2 signaling. Spraque-Dawley rats (SD) were submitted to permanent ligation of the left descending artery (LAD) to induce a MI or to a sham operation. Twenty-four hours, 6 days and 3 weeks after MI, LV function was determined in vivo using a tip catheter. Cardiac IL-2 and IL-1beta content was measured by immunohistochemical staining on cryo-fixed heart cross sections at 24h and 6 days post MI. Total collagen content of the LV was determined by Sirius red stained formalin-stored sections under circularly polarized light 3 weeks post MI. Compared to sham-operated animals, IL-2 content was increased 13-fold (P<0.01) 24h post MI and 16-fold (P<0.01) 6 days post MI in the infarction area as well as 2-fold (P<0.05) 6 days post MI in the non-infarction area. Despite similar infarct sizes, LV function and remodeling were ameliorated in IL-2 fusion protein-treated ischemic rats, indicated by improved LV pressure (LVP), contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)) at all three time points. LV collagen content as a surrogate parameter for remodeling and IL-1beta expression as a marker for myocardial inflammation were reduced in the non-infarcted LV, but not in the LV infarction area compared to vehicle-treated controls. LV contractile dysfunction after experimental MI is improved after treatment with an IL-2-IgG2b fusion protein.
authors.affiliation: Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Koch
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Savvatis
authors.forename: Michael
authors.initials: M
authors.lastname: Scheeler
authors.forename: Sameer
authors.initials: S
authors.lastname: Dhayat
authors.forename: Klaus
authors.initials: K
authors.lastname: Bonaventura
authors.forename: Thomas
authors.initials: T
authors.lastname: Pohl
authors.forename: Alexander
authors.initials: A
authors.lastname: Riad
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulfone-Paus
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
mesh_terms: D000818:Animals; D005355:Fibrosis; D006439:Hemodynamics; D007074:Immunoglobulin G / Q000235:genetics / Q000627:therapeutic use*; D007165:Immunosuppression Therapy / Q000379:methods*; D007375:Interleukin-1 / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D007074:Immunoglobulin G; D007375:Interleukin-1; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins