Abstract 1123: Interleukin (IL)-11 Prevents Ischemia/Reperfusion Injury in Hearts as a Novel Cardioprotective Cytokine
Background: IL-11, a pleiotropic member of the IL-6 cytokine family, is known to be expressed in cardiac myocytes. Though recent studies have demonstrated these cytokines directly transduce the signals responsible for cardiac homeostasis in cardiomyocytes, the biological significance of IL-11 remains to be elucidated. Here we studied the effects of IL-11 on cardiac function in order to investigate whether IL-11 can be applied to treat cardiovascular disease. This would be an asset since IL-11 is clinically available and currently used in the treatment of chemotherapy-induced thrombocytopenia.
Methods and Results: IL-11 receptor expression was confirmed in rat neonatal cardiomyocytes by RT-PCR analyses. Immunoblotting analyses revealed that stimulation with IL-11 rapidly phosphorylated both STAT3 and ERK 1/2 reaching a peak within 15 min (n=4, P<0.05 each), and these effects were submaximally observed at 20 ng/ml (n=4, P<0.05 each). IL-11 (20 ng/ml) induced cardiac hypertrophy in cultured cardiomyocytes increasing cell surface area by 22 ± 14 % and the cell length (long axis) by 43 ± 7 % compared with controls (n=151–227, P<0.05 each). Importantly, cardiomyocytes cultured with IL-11 (20 ng/ml) exhibited a 2.0 ± 0.2 fold higher (P<0.05, n=8) activity to metabolize MTS under serum-depleted conditions suggesting a cytoprotective property of IL-11. In vivo, C57Bl/6 mice were intravenously administered IL-11 (8μg/kg) and exposed to ischemia/reperfusion (I/R) 18 h after injection. Triphenyltetrazolium chloride staining demonstrated a decrease in infarct size (48.1 ± 15.6% vs. 18.5 ± 13.6%, P<0.05), while Evans Blue staining exhibited no significant difference in area at risk in controls (n=9) versus IL-11-treated mice (n=8). Northern blotting analyses revealed that the scavengers for reactive oxygen species (ROS) including metallothionein were remarkably upregulated in IL-11-treated hearts (n=3, P<0.05 vs. controls, each). These results suggest that IL-11 contributes to the resistance of I/R mediated cytoprotective signals and activated ROS scavengers.
Conclusions: IL-11 induces ROS scavengers and mediates cytoprotective signals in murine hearts. IL-11 treatment could be a promising strategy as a cytokine therapy in cardiovascular disease.