Abstract 17799: Role Of Interleukin-1 In Acute Radiation-induced Cardiomyopathy
Background: Mediastinal irradiations (XRT) in cancer treatment are associated with development of cardiomyopathy. Radiation-induced cardiomyopathy is characterized by a latent phase. In mice, an impaired contractile reserve arises early after XRT despite a normal resting cardiac function. XRT induces interleukin-1 (IL-1) in the heart and lungs. We propose to investigate the mechanistic role of IL-1 in the development of XRT-induced cardiomyopathy.
Methods: We irradiated (14Gy, single dose) the thorax of C57BL/6J wild type (wt) mice or IL-1 receptor type I knock out mice (IL-1RI KO, which are not responsive to IL-1)(N=12/group). Wt- and KO-sham irradiated mice were used as controls. The serum levels of cardiac Troponin I (cTnI) were measured by ELISA 3 days after XRT and RT-PCR was used to measure IL-1 beta (IL-1β) mRNA. Left ventricular (LV) ejection fraction (EF) was evaluated by echocardiography at baseline and 3 days following XRT. The beta-adrenergic receptor agonist isoproterenol (10 ng/mouse) was used to measure the contractile reserve (LVEF change).
Results: XRT induced IL-1β mRNA in wt compared to sham-irradiated mice (data not shown). Serum levels of cTnI after XRT were significantly lower in KO vs wt mice (1.04±0.4 ng/ml KO vs 4.6±1.5 ng/ml wt, P=0.037, Figure A). Resting LVEF at 3 days was unchanged in both wt and IL-1RI KO mice after XRT, whereas contractile reserve was significantly reduced in wt but not in KO mice (+16.0±4.1% wt vs +28.6±3.0% KO; P=0.046, Figure B).
Conclusions: IL-1 amplifies myocardial damage during the acute phase of XRT-induced cardiomyopathy. IL-1 blockade may represent a novel therapeutic strategy to protect the heart following XRT. .
- © 2012 by American Heart Association, Inc.