IL-6

IL-6 (interleukin-6) is a cytokine that drives the acute-phase inflammatory response and, when produced chronically, sustains inflammation-associated cancer and aging.

Function

IL-6 is secreted by macrophages, T cells, and stromal cells in response to infection and tissue damage. It signals through a receptor complex that activates JAK kinases and STAT3 - the classical signaling mode in immune cells - and through a second mode (trans-signaling through soluble IL-6 receptor) that reaches cells lacking the membrane receptor, including endothelium and fibroblasts. Its acute-phase outputs are fever induction, hepatocyte production of CRP and fibrinogen, B-cell maturation, and Th17 differentiation.

In cancer and aging

Chronic IL-6 production is common in the tumor microenvironment: stromal and immune cells in inflamed tissue produce IL-6, STAT3 activation in premalignant cells promotes survival and immune evasion, and the feedback loop between inflammation and malignancy is self-sustaining. Senescent cells secrete IL-6 as a core component of the SASP, which makes IL-6 one of the molecular links between senescence, chronic inflammation, and late-life cancer risk. Tocilizumab, an IL-6 receptor antibody, is approved for rheumatoid arthritis and is being studied in cytokine-release syndrome.

Notes

• Human gene symbol: IL6; UniProt P05231; 212 amino acids (precursor); IL-6 cytokine family.