IL-6 (Interleukin-6)

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by immune cells, adipocytes, endothelial cells, and senescent cells that signals through the membrane-bound IL-6 receptor (classical signalling) or through soluble IL-6 receptor trans-signalling, with distinct tissue effects. Acutely, IL-6 is a key inducer of the hepatic acute-phase response — driving CRP, fibrinogen, and serum amyloid A synthesis — and plays an essential role in host defence; after vigorous exercise, skeletal muscle transiently secretes high amounts, reflecting a myokine function. Chronically elevated circulating IL-6, as seen in chronic inflammatory conditions, obesity, and biological aging (inflammaging), is an independent predictor of all-cause and cardiovascular mortality across multiple large prospective cohorts, with prognostic value that remains significant after adjusting for CRP. In longevity research, IL-6 is a central biomarker of inflammaging and a mechanistic target under investigation, given that IL-6 elevation drives downstream pathways linked to sarcopenia, cognitive decline, frailty, and cancer progression.