Immunosuppression with an interleukin-2 fusion protein leads to improved LV function in experimental ischemic cardiomyopathy

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-1β content was measured by immunohistochemical staining on cryo-fixed heart cross sections at 24 h 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) 24 h 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/dtmax) and relaxation (LVdP/dtmin) at all three time points. LV collagen content as a surrogate parameter for remodeling and IL-1β 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.