Interleukin-6/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis

Abstract

Apoptosis of cardiomyocytes plays an important role in reperfusion injury following myocardial infarction. Conversely, interleukin-6 (IL-6)-a potent cytokine-inhibits myeloma cell apoptosis by activating GP130 through the IL-6 receptor (IL-6R). We hypothesized that the IL-6/soluble IL-6R complex can inhibit myocardial apoptosis, and limit infarct size in reperfused acute myocardial infarction. Anesthetized rats were randomly divided into five groups: sham, coronary occlusion and reperfusion rats administered IL-6/soluble IL-6R complex, IL-6 alone, soluble IL-6R (sIL-6R) alone, or a control vehicle. Rats were subjected to 30 min occlusion of the left coronary artery followed by 3 h reperfusion. After reperfusion, the hearts were excised. For detection and quantification of apoptosis, gel electrophoresis of extracted genomic DNA and TUNEL method of paraffin sections were performed. The percentage of the infarct area was measured using tetrazolium chloride staining. The cardiomyocyte apoptosis analysis revealed that apoptosis in the reperfused myocardium was inhibited only in the complex group. Furthermore, the percentage of the infarct area out of the area at risk was remarkably reduced in the complex group (23.871.8%), compared with that in the vehicle (37.973.7%), the IL-6 (40.771.0%), or the sIL-6R (37.572.4%) groups (P ¼ 0.0002). No significant differences were observed among the vehicle, IL-6, and sIL-6R groups. The IL-6/soluble IL-6 receptor complex inhibits cardiomyocyte apoptosis in reperfused acute myocardial infarction. It possibly reduces irreversible reperfusion injury.

Association of NT-proBNP and interleukin-17 levels with heart failure in elderly patients

“…After ischemia reperfusion, injection of IL-17/soluble IL-17R complex prevents myocardial apoptosis and reduces the size of the myocardial infarct. This indicates the protective effect of IL-17 (Matsushita et al, 2005).…”

Changes in Expression of Interleukin-6 Receptors in Granulosa Cells During Follicular Atresia in Pig Ovaries

“…In osteoblasts, IL-6Rα is non-functional and interaction between IL-6 and IL-6sR induces gp130 activation [37]. In rats, administration of IL-6 and IL-6sR, but not IL-6 or IL-6sR alone, inhibits myocardial apoptosis [38]. Therefore, IL-6Rα might transduce different signals from IL-6sR in granulosa cells.…”

Evans Blue Staining of Cardiomyocytes Induced by Myocardial Contrast Echocardiography in Rats: Evidence for Necrosis Instead of Apoptosis

“…Epon imbedded samples were cut for 70 nm sections, which were stained with uranyl acetate and lead citrate for final viewing. The electron microscopy was particularly useful for assessing the contraction band necrosis and the possible chromatin condensation at the margin of the nucleus, which occurs for apoptosis (see, for example, Matsushita et al 2005). …”

“…Apoptosis has been identified in various cardiac disease states, for example, in ischemia and reperfusion injury (Krijnen et al 2002;Eefting et al 2004;Matsushita et al 2005;Liang et al 2006) or doxorubicin toxicity (Ueno et al 2006). Evans blue staining of myocytes has been associated with apoptosis in muscular dystrophy (Matsuda, 1995).…”