Interleukin-6 signaling, soluble glycoprotein 130, and inflammation in heart failure.
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.
Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, P.B. 4950 Nydalen, 0424, Oslo, Norway, erik.tandberg.askevold@rr-research.no.
Erik Tandberg
ET
Askevold
Lars
L
Gullestad
Christen P
CP
Dahl
Arne
A
Yndestad
Thor
T
Ueland
Pål
P
Aukrust
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D050822:Cytokine Receptor gp130 / Q000097:blood*; D006023:Glycoproteins / Q000097:blood / Q000276:immunology*; D006333:Heart Failure / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001688:Biological Products; D015415:Biomarkers; D006023:Glycoproteins; D015850:Interleukin-6; C480482:glycoprotein 130, human; D050822:Cytokine Receptor gp130