Interleukin-6 signaling, soluble glycoprotein 130, and inflammation in heart failure

Abstract

Both experimental and clinical evidence accumulated over the last couple of decades has linked inflammatory activation to the initiation and progression of chronic heart failure (HF). Circulating levels of inflammatory mediators are associated with cardiac function and inform risk prediction in patients, but the effect of anti-inflammatory therapy in HF remains uncertain. Interleukin (IL)-6 type cytokines are central to the inflammatory response, and convey their signals through the ubiquitously expressed glycoprotein (gp) 130 receptor subunit. IL-6-type/gp130 signaling therefore represents an inflammatory nexus, with inherent potential for disease modification. This review focuses on the current knowledge of IL-6/gp130 signaling in relation to HF, with a particular emphasis on the role of soluble gp130 (sgp130), a signaling pathway modulator. Biological aspects of sgp130 and IL-6 signaling are discussed, as are potential novel therapeutic approaches to modulate this central inflammatory signaling pathway.